Generic placeholder image

Current Pharmaceutical Design

Author(s): Patricia R. Manzine, Izabela P. Vatanabe, Rafaela Peron, Marina M. Grigoli, Renata V. Pedroso, Carla M.C. Nascimento and Marcia R. Cominetti*

DOI: 10.2174/1381612826666200114105515

DownloadDownload PDF Flyer Cite As
Blood-based Biomarkers of Alzheimer’s Disease: The Long and Winding Road

Page: [1300 - 1315] Pages: 16

  • * (Excluding Mailing and Handling)

Abstract

Background: Blood-based biomarkers can be very useful in formulating new diagnostic and treatment proposals in the field of dementia, especially in Alzheimer’s disease (AD). However, due to the influence of several factors on the reproducibility and reliability of these markers, their clinical use is still very uncertain. Thus, up-to-date knowledge about the main blood biomarkers that are currently being studied is extremely important in order to discover clinically useful and applicable tools, which could also be used as novel pharmacological strategies for the AD treatment.

Methods: A narrative review was performed based on the current candidates of blood-based biomarkers for AD to show the main results from different studies, focusing on their clinical applicability and association with AD pathogenesis.

Objective: The aim of this paper was to carry out a literature review on the major blood-based biomarkers for AD, connecting them with the pathophysiology of the disease.

Results: Recent advances in the search of blood-based AD biomarkers were summarized in this review. The biomarkers were classified according to the topics related to the main hallmarks of the disease such as inflammation, amyloid, and tau deposition, synaptic degeneration and oxidative stress. Moreover, molecules involved in the regulation of proteins related to these hallmarks were described, such as non-coding RNAs, neurotrophins, growth factors and metabolites. Cells or cellular components with the potential to be considered as blood-based AD biomarkers were described in a separate topic.

Conclusion: A series of limitations undermine new discoveries on blood-based AD biomarkers. The lack of reproducibility of findings due to the small size and heterogeneity of the study population, different analytical methods and other assay conditions make longitudinal studies necessary in this field to validate these structures, especially when considering a clinical evaluation that includes a broad panel of these potential and promising blood-based biomarkers.

Keywords: Alzheimer's disease, biomarkers, blood, dementia, diagnosis, elderly, plasma.

[1]
Sperling R, Mormino E, Johnson K. The evolution of preclinical Alzheimer’s disease: implications for prevention trials. Neuron 2014; 84(3): 608-22.
[http://dx.doi.org/10.1016/j.neuron.2014.10.038] [PMID: 25442939]
[2]
Wren MC, Lashley T, Årstad E, Sander K. Large inter- and intra-case variability of first generation tau PET ligand binding in neurodegenerative dementias. Acta Neuropathol Commun 2018; 6(1): 34.
[http://dx.doi.org/10.1186/s40478-018-0535-z] [PMID: 29716656]
[3]
O’Bryant SE, Mielke MM, Rissman RA, et al. Biofluid Based Biomarker Professional Interest Area.Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic. Alzheimers Dement 2017; 13(1): 45-58.
[http://dx.doi.org/10.1016/j.jalz.2016.09.014] [PMID: 27870940]
[4]
O’Bryant SE, Gupta V, Henriksen K, et al. STAR-B and BBBIG working groups.Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer’s disease research. Alzheimers Dement 2015; 11(5): 549-60.
[http://dx.doi.org/10.1016/j.jalz.2014.08.099] [PMID: 25282381]
[5]
Giunta B, Fernandez F, Nikolic WV, et al. Inflammaging as a prodrome to Alzheimer’s disease. J Neuroinflammation 2008; 5: 51.
[http://dx.doi.org/10.1186/1742-2094-5-51] [PMID: 19014446]
[6]
Popp J, Oikonomidi A, Tautvydaitė D, et al. Markers of neuroinflammation associated with Alzheimer’s disease pathology in older adults. Brain Behav Immun 2017; 62: 203-11.
[http://dx.doi.org/10.1016/j.bbi.2017.01.020] [PMID: 28161476]
[7]
Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 2015; 14(4): 388-405.
[http://dx.doi.org/10.1016/S1474-4422(15)70016-5] [PMID: 25792098]
[8]
Neher JJ, Cunningham C. Priming microglia for innate immune memory in the brain. Trends Immunol 2019; 40(4): 358-74.
[http://dx.doi.org/10.1016/j.it.2019.02.001] [PMID: 30833177]
[9]
Combs CK, Karlo JC, Kao SC, Landreth GE. beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci 2001; 21(4): 1179-88.
[http://dx.doi.org/10.1523/JNEUROSCI.21-04-01179.2001] [PMID: 11160388]
[10]
Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement (N Y) 2018; 4: 575-90.
[http://dx.doi.org/10.1016/j.trci.2018.06.014] [PMID: 30406177]
[11]
Okello A, Edison P, Archer HA, et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 2009; 72(1): 56-62.
[http://dx.doi.org/10.1212/01.wnl.0000338622.27876.0d] [PMID: 19122031]
[12]
De Simoni MG, Sironi M, De Luigi A, Manfridi A, Mantovani A, Ghezzi P. Intracerebroventricular injection of interleukin 1 induces high circulating levels of interleukin 6. J Exp Med 1990; 171(5): 1773-8.
[http://dx.doi.org/10.1084/jem.171.5.1773] [PMID: 2332736]
[13]
Monson NL, Ireland SJ, Ligocki AJ, et al. Elevated CNS inflammation in patients with preclinical Alzheimer’s disease. J Cereb Blood Flow Metab 2014; 34(1): 30-3.
[http://dx.doi.org/10.1038/jcbfm.2013.183] [PMID: 24149932]
[14]
Aisen PS. The potential of anti-inflammatory drugs for the treatment of Alzheimer’s disease. Lancet Neurol 2002; 1(5): 279-84.
[http://dx.doi.org/10.1016/S1474-4422(02)00133-3] [PMID: 12849425]
[15]
Gupta PP, Pandey RD, Jha D, Shrivastav V, Kumar S. Role of traditional nonsteroidal anti-inflammatory drugs in Alzheimer’s disease: a meta-analysis of randomized clinical trials. Am J Alzheimers Dis Other Demen 2015; 30(2): 178-82.
[http://dx.doi.org/10.1177/1533317514542644] [PMID: 25024454]
[16]
Fülöp T, Larbi A, Witkowski JM. Human Inflammaging. Gerontology 2019; 65(5): 495-504.
[http://dx.doi.org/10.1159/000497375] [PMID: 31055573]
[17]
Braz ID, Fisher JP. The impact of age on cerebral perfusion, oxygenation and metabolism during exercise in humans. J Physiol 2016; 594(16): 4471-83.
[http://dx.doi.org/10.1113/JP271081] [PMID: 26435295]
[18]
McNaull BB, Todd S, McGuinness B, Passmore AP. Inflammation and anti-inflammatory strategies for Alzheimer’s disease--a mini-review. Gerontology 2010; 56(1): 3-14.
[http://dx.doi.org/10.1159/000237873] [PMID: 19752507]
[19]
Fougère B, Boulanger E, Nourhashémi F, Guyonnet S, Cesari M. Chronic inflammation: accelerator of biological aging. J Gerontol A Biol Sci Med Sci 2017; 72(9): 1218-25.
[http://dx.doi.org/10.1093/gerona/glw240] [PMID: 28003373]
[20]
King E, O’Brien JT, Donaghy P, et al. Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias. J Neurol Neurosurg Psychiatry 2018; 89(4): 339-45.
[http://dx.doi.org/10.1136/jnnp-2017-317134] [PMID: 29248892]
[21]
Cherbuin N, Walsh E, Baune BT, Anstey KJ. Oxidative stress, inflammation and risk of neurodegeneration in a population sample. Eur J Neurol 2019; 26(11): 1347-54.
[http://dx.doi.org/10.1111/ene.13985] [PMID: 31081571]
[22]
Tarasoff-Conway JM, Carare RO, Osorio RS, et al. Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol 2015; 11(8): 457-70.
[http://dx.doi.org/10.1038/nrneurol.2015.119] [PMID: 26195256]
[23]
Olson L, Humpel C. Growth factors and cytokines/chemokines as surrogate biomarkers in cerebrospinal fluid and blood for diagnosing Alzheimer’s disease and mild cognitive impairment. Exp Gerontol 2010; 45(1): 41-6.
[http://dx.doi.org/10.1016/j.exger.2009.10.011] [PMID: 19853649]
[24]
Alcolea D, Martínez-Lage P, Sánchez-Juan P, et al. Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology 2015; 85(7): 626-33.
[http://dx.doi.org/10.1212/WNL.0000000000001859] [PMID: 26180139]
[25]
Tejera D, Heneka MT. Microglia in Alzheimer’s disease: the good, the bad and the ugly. Curr Alzheimer Res 2016; 13(4): 370-80.
[http://dx.doi.org/10.2174/1567205013666151116125012] [PMID: 26567746]
[26]
Trollor JN, Smith E, Agars E, et al. The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study. Age (Dordr) 2012; 34(5): 1295-308.
[http://dx.doi.org/10.1007/s11357-011-9301-x] [PMID: 21853262]
[27]
Magaki S, Mueller C, Dickson C, Kirsch W. Increased production of inflammatory cytokines in mild cognitive impairment. Exp Gerontol 2007; 42(3): 233-40.
[http://dx.doi.org/10.1016/j.exger.2006.09.015] [PMID: 17085001]
[28]
Engelhart MJ, Geerlings MI, Meijer J, et al. Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol 2004; 61(5): 668-72.
[http://dx.doi.org/10.1001/archneur.61.5.668] [PMID: 15148142]
[29]
Kuo HK, Yen CJ, Chang CH, Kuo CK, Chen JH, Sorond F. Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol 2005; 4(6): 371-80.
[http://dx.doi.org/10.1016/S1474-4422(05)70099-5] [PMID: 15907742]
[30]
Motta M, Imbesi R, Di Rosa M, Stivala F, Malaguarnera L. Altered plasma cytokine levels in Alzheimer’s disease: correlation with the disease progression. Immunol Lett 2007; 114(1): 46-51.
[http://dx.doi.org/10.1016/j.imlet.2007.09.002] [PMID: 17949824]
[31]
Lai KSP, Liu CS, Rau A, et al. Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies. J Neurol Neurosurg Psychiatry 2017; 88(10): 876-82.
[http://dx.doi.org/10.1136/jnnp-2017-316201] [PMID: 28794151]
[32]
Macy EM, Hayes TE, Tracy RP. Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications. Clin Chem 1997; 43(1): 52-8.
[PMID: 8990222]
[33]
Hilal S, Ikram MA, Verbeek MM, et al. C-Reactive protein, plasma amyloid-β levels, and their interaction with magnetic resonance imaging markers. Stroke 2018; 49(11): 2692-8.
[http://dx.doi.org/10.1161/STROKEAHA.118.022317] [PMID: 30355213]
[34]
Perry VH. The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun 2004; 18(5): 407-13.
[http://dx.doi.org/10.1016/j.bbi.2004.01.004] [PMID: 15265532]
[35]
Uslu S, Akarkarasu ZE, Ozbabalik D, et al. Levels of amyloid beta-42, interleukin-6 and tumor necrosis factor-alpha in Alzheimer’s disease and vascular dementia. Neurochem Res 2012; 37(7): 1554-9.
[http://dx.doi.org/10.1007/s11064-012-0750-0] [PMID: 22437436]
[36]
Zuliani G, Ranzini M, Guerra G, et al. Plasma cytokines profile in older subjects with late onset Alzheimer’s disease or vascular dementia. J Psychiatr Res 2007; 41(8): 686-93.
[http://dx.doi.org/10.1016/j.jpsychires.2006.02.008] [PMID: 16600299]
[37]
Brosseron F, Krauthausen M, Kummer M, Heneka MT. Body fluid cytokine levels in mild cognitive impairment and Alzheimer’s disease: a comparative overview. Mol Neurobiol 2014; 50(2): 534-44.
[http://dx.doi.org/10.1007/s12035-014-8657-1] [PMID: 24567119]
[38]
Kreuzer KA, Rockstroh JK, Sauerbruch T, Spengler U. A comparative study of different enzyme immunosorbent assays for human tumor necrosis factor-alpha. J Immunol Methods 1996; 195(1-2): 49-54.
[http://dx.doi.org/10.1016/0022-1759(96)00090-7] [PMID: 8814319]
[39]
Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003; 10(1): 45-65.
[http://dx.doi.org/10.1038/sj.cdd.4401189] [PMID: 12655295]
[40]
Buchhave P, Zetterberg H, Blennow K, Minthon L, Janciauskiene S, Hansson O. Soluble TNF receptors are associated with Aβ metabolism and conversion to dementia in subjects with mild cognitive impairment. Neurobiol Aging 2010; 31(11): 1877-84.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.10.012] [PMID: 19070941]
[41]
Decourt B, Lahiri DK, Sabbagh MN. Targeting tumor necrosis factor alpha for Alzheimer’s disease. Curr Alzheimer Res 2017; 14(4): 412-25.
[PMID: 27697064]
[42]
Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science 1992; 256(5054): 184-5.
[http://dx.doi.org/10.1126/science.1566067] [PMID: 1566067]
[43]
Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 1991; 12(10): 383-8.
[http://dx.doi.org/10.1016/0165-6147(91)90609-V] [PMID: 1763432]
[44]
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002; 297(5580): 353-6.
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[45]
Vassar R, Bennett BD, Babu-Khan S, et al. Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999; 286(5440): 735-41.
[http://dx.doi.org/10.1126/science.286.5440.735] [PMID: 10531052]
[46]
Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 1999; 398(6727): 513-7.
[http://dx.doi.org/10.1038/19077] [PMID: 10206644]
[47]
Folch J, Petrov D, Ettcheto M, et al. Current research therapeutic strategies for Alzheimer’s disease treatment. Neural Plast 2016; 2016 8501693
[http://dx.doi.org/10.1155/2016/8501693] [PMID: 26881137]
[48]
Zetterberg H, Andreasson U, Hansson O, et al. Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease. Arch Neurol 2008; 65(8): 1102-7.
[http://dx.doi.org/10.1001/archneur.65.8.1102] [PMID: 18695061]
[49]
Portelius E, Price E, Brinkmalm G, et al. A novel pathway for amyloid precursor protein processing. Neurobiol Aging 2011; 32(6): 1090-8.
[http://dx.doi.org/10.1016/j.neurobiolaging.2009.06.002] [PMID: 19604603]
[50]
Hölttä M, Hansson O, Andreasson U, et al. Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer’s disease. PLoS One 2013; 8(6) e66381
[http://dx.doi.org/10.1371/journal.pone.0066381] [PMID: 23799095]
[51]
Savage MJ, Kalinina J, Wolfe A, et al. A sensitive aβ oligomer assay discriminates Alzheimer’s and aged control cerebrospinal fluid. J Neurosci 2014; 34(8): 2884-97.
[http://dx.doi.org/10.1523/JNEUROSCI.1675-13.2014] [PMID: 24553930]
[52]
Blennow K, Hampel H, Zetterberg H. Biomarkers in amyloid-beta immunotherapy trials in Alzheimer's diseaseNeuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 2014; 39(1): 189-201.
[53]
Blennow K, Mattsson N, Schöll M, Hansson O, Zetterberg H. Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol Sci 2015; 36(5): 297-309.
[http://dx.doi.org/10.1016/j.tips.2015.03.002] [PMID: 25840462]
[54]
Jack CR Jr, Therneau TM, Wiste HJ, et al. Transition rates between amyloid and neurodegeneration biomarker states and to dementia: a population-based, longitudinal cohort study. Lancet Neurol 2016; 15(1): 56-64.
[http://dx.doi.org/10.1016/S1474-4422(15)00323-3] [PMID: 26597325]
[55]
Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010; 6(3): 131-44.
[http://dx.doi.org/10.1038/nrneurol.2010.4] [PMID: 20157306]
[56]
Noelker C, Hampel H, Dodel R. Blood-based protein biomarkers for diagnosis and classification of neurodegenerative diseases: current progress and clinical potential. Mol Diagn Ther 2011; 15(2): 83-102.
[http://dx.doi.org/10.1007/BF03256398] [PMID: 21623645]
[57]
Bazenet C, Lovestone S. Plasma biomarkers for Alzheimer’s disease: much needed but tough to find. Biomarkers Med 2012; 6(4): 441-54.
[http://dx.doi.org/10.2217/bmm.12.48] [PMID: 22917146]
[58]
Henriksen K, O’Bryant SE, Hampel H, et al. Blood-Based Biomarker Interest Group.The future of blood-based biomarkers for Alzheimer’s disease. Alzheimers Dement 2014; 10(1): 115-31.
[http://dx.doi.org/10.1016/j.jalz.2013.01.013] [PMID: 23850333]
[59]
Blasko I, Jellinger K, Kemmler G, et al. Conversion from cognitive health to mild cognitive impairment and Alzheimer’s disease: prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine. Neurobiol Aging 2008; 29(1): 1-11.
[http://dx.doi.org/10.1016/j.neurobiolaging.2006.09.002] [PMID: 17055615]
[60]
Graff-Radford NRC, Crook JE, Lucas J, et al. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol 2007; 64(3): 354-62.
[http://dx.doi.org/10.1001/archneur.64.3.354] [PMID: 17353377]
[61]
Wang MJ, Yi S, Han JY, et al. Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease. Alzheimers Res Ther 2017; 9(1): 98.
[http://dx.doi.org/10.1186/s13195-017-0324-0] [PMID: 29246249]
[62]
Nabers A, Perna L, Lange J, et al. Amyloid blood biomarker detects Alzheimer’s disease. EMBO Mol Med 2018; 10(5) e8763
[http://dx.doi.org/10.15252/emmm.201708763] [PMID: 29626112]
[63]
Nabers A, Hafermann H, Wiltfang J, Gerwert K. Aβ and tau structure-based biomarkers for a blood- and CSF-based two-step recruitment strategy to identify patients with dementia due to Alzheimer’s disease. Alzheimers Dement (Amst) 2019; 11: 257-63.
[http://dx.doi.org/10.1016/j.dadm.2019.01.008] [PMID: 30911600]
[64]
Palmqvist S, Janelidze S, Stomrud E, et al. Performance of fully automated plasma assays as screening tests for alzheimer disease-related β-amyloid statusJAMA Neurol 2019. (Epub ahed of print).
[http://dx.doi.org/10.1001/jamaneurol.2019.1632 ] [PMID: 31233127]
[65]
Chatterjee P, Elmi M, Goozee K, et al. Ultrasensitive detection of plasma amyloid-β as a biomarker for cognitively normal elderly individuals at risk of Alzheimer’s disease. J Alzheimers Dis 2019; 71(3): 775-83.
[http://dx.doi.org/10.3233/JAD-190533] [PMID: 31424403]
[66]
Vergallo A, Mégret L, Lista S, et al. INSIGHT-preAD study group.Alzheimer Precision Medicine Initiative (APMI).Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer’s disease. Alzheimers Dement 2019; 15(6): 764-75.
[http://dx.doi.org/10.1016/j.jalz.2019.03.009] [PMID: 31113759]
[67]
Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol 2018; 25(1): 59-70.
[http://dx.doi.org/10.1111/ene.13439] [PMID: 28872215]
[68]
Slachevsky A, Guzmán-Martínez L, Delgado C, et al. Tau Platelets correlate with regional brain atrophy in patients with Alzheimer ’s disease. J Alzheimers Dis 2017; 55(4): 1595-603.
[http://dx.doi.org/10.3233/JAD-160652] [PMID: 27911301]
[69]
Guzmán-Martínez L, Tapia JP, Farías GA, González A, Estrella M, Maccioni RB. The alz-tau biomarker for Alzheimer’s disease: study in a caucasian population. J Alzheimers Dis 2019; 67(4): 1181-6.
[http://dx.doi.org/10.3233/JAD-180637] [PMID: 30775977]
[70]
Mukaetova-Ladinska E, Abdell-All Z, Andrade J, Alves da Silva J, Boksha I, Burbaeva G. Platelet tau protein as a potential peripheral biomarker in alzheimer’s disease: an explorative study 2018; 15(9) 800-8.
[71]
Park JC, Han SH, Yi D, et al. Plasma tau/amyloid-β1-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease. Brain 2019; 142(3): 771-86.
[http://dx.doi.org/10.1093/brain/awy347] [PMID: 30668647]
[72]
Chen Z, Mengel D, Keshavan A, et al. Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer’s disease. Alzheimers Dement 2019; 15(3): 487-96.
[http://dx.doi.org/10.1016/j.jalz.2018.09.010] [PMID: 30419228]
[73]
Skaper SD. The biology of neurotrophins, signalling pathways, and functional peptide mimetics of neurotrophins and their receptors. CNS Neurol Disord Drug Targets 2008; 7(1): 46-62.
[http://dx.doi.org/10.2174/187152708783885174] [PMID: 18289031]
[74]
Balietti M, Giuli C, Conti F. Peripheral blood brain-derived neurotrophic factor as a biomarker of Alzheimer’s disease: are there methodological biases? Mol Neurobiol 2018; 55(8): 6661-72.
[http://dx.doi.org/10.1007/s12035-017-0866-y] [PMID: 29330839]
[75]
Song JH, Yu JT, Tan L. Brain-derived neurotrophic factor in alzheimer’s disease: risk, mechanisms, and therapy. Mol Neurobiol 2015; 52(3): 1477-93.
[http://dx.doi.org/10.1007/s12035-014-8958-4] [PMID: 25354497]
[76]
Angelucci F, Spalletta G, di Iulio F, et al. Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) patients are characterized by increased BDNF serum levels. Curr Alzheimer Res 2010; 7(1): 15-20.
[http://dx.doi.org/10.2174/156720510790274473] [PMID: 20205668]
[77]
Faria MC, Gonçalves GS, Rocha NP, et al. Increased plasma levels of BDNF and inflammatory markers in Alzheimer’s disease. J Psychiatr Res 2014; 53: 166-72.
[http://dx.doi.org/10.1016/j.jpsychires.2014.01.019] [PMID: 24576746]
[78]
Liu YH, Jiao SS, Wang YR, et al. Associations between ApoEε4 carrier status and serum BDNF levels--new insights into the molecular mechanism of ApoEε4 actions in Alzheimer’s disease. Mol Neurobiol 2015; 51(3): 1271-7.
[http://dx.doi.org/10.1007/s12035-014-8804-8] [PMID: 24986007]
[79]
Passaro A, Dalla Nora E, Morieri ML, et al. Brain-derived neurotrophic factor plasma levels: relationship with dementia and diabetes in the elderly population. J Gerontol A Biol Sci Med Sci 2015; 70(3): 294-302.
[http://dx.doi.org/10.1093/gerona/glu028] [PMID: 24621946]
[80]
Janel N, Alexopoulos P, Badel A, et al. Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer’s disease. Transl Psychiatry 2017; 7(6) e1154
[http://dx.doi.org/10.1038/tp.2017.123] [PMID: 28632203]
[81]
Woolley JD, Strobl EV, Shelly WB, et al. BDNF serum concentrations show no relationship with diagnostic group or medication status in neurodegenerative disease. Curr Alzheimer Res 2012; 9(7): 815-21.
[http://dx.doi.org/10.2174/156720512802455395] [PMID: 21605064]
[82]
Alvarez A, Aleixandre M, Linares C, Masliah E, Moessler H. Apathy and APOE4 are associated with reduced BDNF levels in Alzheimer’s disease. J Alzheimers Dis 2014; 42(4): 1347-55.
[http://dx.doi.org/10.3233/JAD-140849] [PMID: 25024337]
[83]
Du Y, Wu HT, Qin XY, et al. Postmortem brain, cerebrospinal fluid, and blood neurotrophic factor levels in Alzheimer’s disease: a systematic review and meta-analysis. J Mol Neurosci 2018; 65(3): 289-300.
[http://dx.doi.org/10.1007/s12031-018-1100-8]
[84]
Ng TKS, Ho CSH, Tam WWS, Kua EH, Ho RC. Decreased serum brain-derived neurotrophic factor (BDNF) levels in patients with Alzheimer’s disease (AD): a systematic review and meta-analysis. Int J Mol Sci 2019; 20(2) E257
[http://dx.doi.org/10.3390/ijms20020257] [PMID: 30634650]
[85]
Crispoltoni L, Stabile AM, Pistilli A, et al. Changes in plasma β-ngf and its receptors expression on peripheral blood monocytes during Alzheimer’s disease progression. J Alzheimers Dis 2017; 55(3): 1005-17.
[http://dx.doi.org/10.3233/JAD-160625] [PMID: 27802234]
[86]
Gubbi S, Quipildor GF, Barzilai N, Huffman DM, Milman S. 40 YEARS of IGF1: IGF1: the Jekyll and Hyde of the aging brain. J Mol Endocrinol 2018; 61(1): T171-85.
[http://dx.doi.org/10.1530/JME-18-0093] [PMID: 29739805]
[87]
de Bruijn RF, Janssen JA, Brugts MP, et al. Insulin-like growth factor-I receptor stimulating activity is associated with dementia. J Alzheimers Dis 2014; 42(1): 137-42.
[http://dx.doi.org/10.3233/JAD-140186] [PMID: 24820016]
[88]
Galle SA, van der Spek A, Drent ML, et al. Revisiting the role of insulin-like growth factor-i receptor stimulating activity and the apolipoprotein e in Alzheimer’s disease. Front Aging Neurosci 2019; 11(20): 20.
[http://dx.doi.org/10.3389/fnagi.2019.00020] [PMID: 30809143]
[89]
Toledo JB, Arnold M, Kastenmüller G, et al. Alzheimer’s Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium.Metabolic network failures in Alzheimer’s disease: A biochemical road map. Alzheimers Dement 2017; 13(9): 965-84.
[http://dx.doi.org/10.1016/j.jalz.2017.01.020] [PMID: 28341160]
[90]
Varma VR, Oommen AM, Varma S, et al. Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study. PLoS Med 2018; 15(1) e1002482
[http://dx.doi.org/10.1371/journal.pmed.1002482] [PMID: 29370177]
[91]
Mielke MM, Bandaru VV, Haughey NJ, et al. Serum ceramides increase the risk of Alzheimer disease: the Women’s Health and Aging Study II. Neurology 2012; 79(7): 633-41.
[http://dx.doi.org/10.1212/WNL.0b013e318264e380] [PMID: 22815558]
[92]
Whiley L, Sen A, Heaton J, et al. AddNeuroMed Consortium.Evidence of altered phosphatidylcholine metabolism in Alzheimer’s disease. Neurobiol Aging 2014; 35(2): 271-8.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.08.001] [PMID: 24041970]
[93]
Kim M, Nevado-Holgado A, Whiley L, et al. Association between plasma ceramides and phosphatidylcholines and hippocampal brain volume in late onset alzheimer’s disease. J Alzheimers Dis 2017; 60(3): 809-17.
[http://dx.doi.org/10.3233/JAD-160645] [PMID: 27911300]
[94]
Fiandaca MS, Zhong X, Cheema AK, et al. Plasma 24-metabolite panel predicts preclinical transition to clinical stages of Alzheimer’s disease. Front Neurol 2015; 6: 237.
[http://dx.doi.org/10.3389/fneur.2015.00237] [PMID: 26617567]
[95]
Martínez-Morillo E, Hansson O, Atagi Y, et al. Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer’s disease patients and controls. Acta Neuropathol 2014; 127(5): 633-43.
[http://dx.doi.org/10.1007/s00401-014-1266-2] [PMID: 24633805]
[96]
Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Plasma apolipoprotein E levels and risk of dementia: A Mendelian randomization study of 106,562 individuals. Alzheimers Dement 2018; 14(1): 71-80.
[http://dx.doi.org/10.1016/j.jalz.2017.05.006] [PMID: 28774656]
[97]
Safieh M, Korczyn AD, Michaelson DM. ApoE4: an emerging therapeutic target for Alzheimer’s disease. BMC Med 2019; 17(1): 64.
[http://dx.doi.org/10.1186/s12916-019-1299-4] [PMID: 30890171]
[98]
Weinstein G, Beiser AS, Preis SR, et al. Plasma clusterin levels and risk of dementia, Alzheimer’s disease, and stroke. Alzheimers Dement (Amst) 2016; 3: 103-9.
[http://dx.doi.org/10.1016/j.dadm.2016.06.005] [PMID: 27453932]
[99]
Gupta VB, Hone E, Pedrini S, et al. AIBL Research Group.Altered levels of blood proteins in Alzheimer’s disease longitudinal study: Results from Australian Imaging Biomarkers Lifestyle Study of Ageing cohort. Alzheimers Dement (Amst) 2017; 8: 60-72.
[http://dx.doi.org/10.1016/j.dadm.2017.04.003] [PMID: 28508031]
[100]
Klavins K, Koal T, Dallmann G, Marksteiner J, Kemmler G, Humpel C. The ratio of phosphatidylcholines to lysophosphatidylcholines in plasma differentiates healthy controls from patients with Alzheimer’s disease and mild cognitive impairment. Alzheimers Dement (Amst) 2015; 1(3): 295-302.
[http://dx.doi.org/10.1016/j.dadm.2015.05.003] [PMID: 26744734]
[101]
Graham SF, Chevallier OP, Elliott CT, et al. Untargeted metabolomic analysis of human plasma indicates differentially affected polyamine and L-arginine metabolism in mild cognitive impairment subjects converting to Alzheimer’s disease. PLoS One 2015; 10(3) e0119452
[http://dx.doi.org/10.1371/journal.pone.0119452] [PMID: 25803028]
[102]
Bahnasy WE-H YA, El-Seidy EA. Sex hormones and Alzheimer’s Disease 2017.
[103]
Scheyer O, Rahman A, Hristov H, et al. Female sex and alzheimer’s risk: the menopause connection. J Prev Alzheimers Dis 2018; 5(4): 225-30.
[PMID: 30298180]
[104]
Gouras GK, Xu H, Gross RS, et al. Testosterone reduces neuronal secretion of Alzheimer’s β-amyloid peptides. Proc Natl Acad Sci USA 2000; 97(3): 1202-5.
[http://dx.doi.org/10.1073/pnas.97.3.1202] [PMID: 10655508]
[105]
Wang S, Wang R, Chen L, Bennett DA, Dickson DW, Wang DS. Expression and functional profiling of neprilysin, insulin-degrading enzyme, and endothelin-converting enzyme in prospectively studied elderly and Alzheimer’s brain. J Neurochem 2010; 115(1): 47-57.
[http://dx.doi.org/10.1111/j.1471-4159.2010.06899.x] [PMID: 20663017]
[106]
Cheng Z, Yin J, Yuan H, et al. Blood-derived plasma protein biomarkers for Alzheimer’s disease in han Chinese. Front Aging Neurosci 2018; 10: 414.
[http://dx.doi.org/10.3389/fnagi.2018.00414] [PMID: 30618720]
[107]
Schindler N, Mayer J, Saenger S, et al. Phenotype analysis of male transgenic mice overexpressing mutant IGFBP-2 lacking the Cardin-Weintraub sequence motif: Reduced expression of synaptic markers and myelin basic protein in the brain and a lower degree of anxiety-like behaviour. Growth Horm IGF Res 2017; 33: 1-8.
[108]
Tham A, Nordberg A, Grissom FE, Carlsson-Skwirut C, Viitanen M, Sara VR. Insulin-like growth factors and insulin-like growth factor binding proteins in cerebrospinal fluid and serum of patients with dementia of the Alzheimer type. J Neural Transm Park Dis Dement Sect 1993; 5(3): 165-76.
[http://dx.doi.org/10.1007/BF02257671] [PMID: 7690227]
[109]
McLimans KE, Webb JL, Anantharam V, Kanthasamy A, Willette AA. Alzheimer’s disease neuroimaging initiative. peripheral versus central index of metabolic dysfunction and associations with Clinical and Pathological Outcomes in Alzheimer’s Disease. J Alzheimers Dis 2017; 60(4): 1313-24.
[http://dx.doi.org/10.3233/JAD-170263] [PMID: 28968233]
[110]
Bennett S, Grant M, Creese AJ, et al. Plasma levels of complement 4a protein are increased in Alzheimer’s disease. Alzheimer Dis Assoc Disord 2012; 26(4): 329-34.
[http://dx.doi.org/10.1097/WAD.0b013e318239dcbd] [PMID: 22052466]
[111]
Uchida K, Shan L, Suzuki H, et al. Amyloid-β sequester proteins as blood-based biomarkers of cognitive decline. Alzheimers Dement (Amst) 2015; 1(2): 270-80.
[http://dx.doi.org/10.1016/j.dadm.2015.04.003] [PMID: 27239510]
[112]
Petzold A. Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J Neurol Sci 2005; 233(1-2): 183-98.
[http://dx.doi.org/10.1016/j.jns.2005.03.015] [PMID: 15896809]
[113]
Lewczuk P, Ermann N, Andreasson U, et al. Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther 2018; 10(1): 71.
[http://dx.doi.org/10.1186/s13195-018-0404-9] [PMID: 30055655]
[114]
Blennow K. A review of fluid biomarkers for Alzheimer’s disease: Moving from CSF to Blood. Neurol Ther 2017; 6(Suppl. 1): 15-24.
[http://dx.doi.org/10.1007/s40120-017-0073-9] [PMID: 28733960]
[115]
Weston PSJ, Poole T, Ryan NS, et al. Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration. Neurology 2017; 89(21): 2167-75.
[http://dx.doi.org/10.1212/WNL.0000000000004667] [PMID: 29070659]
[116]
Yao F, Zhang K, Zhang Y, et al. Identification of blood biomarkers for alzheimer’s disease through computational prediction and experimental validation. Front Neurol 2019; 9: 1158.
[http://dx.doi.org/10.3389/fneur.2018.01158] [PMID: 30671019]
[117]
Mroczko B, Groblewska M, Zboch M, et al. Concentrations of matrix metalloproteinases and their tissue inhibitors in the cerebrospinal fluid of patients with Alzheimer’s disease. J Alzheimers Dis 2014; 40(2): 351-7.
[http://dx.doi.org/10.3233/JAD-131634] [PMID: 24448781]
[118]
Hernández-Guillamon M, Delgado P, Ortega L, et al. Neuronal TIMP-1 release accompanies astrocytic MMP-9 secretion and enhances astrocyte proliferation induced by beta-amyloid 25-35 fragment. J Neurosci Res 2009; 87(9): 2115-25.
[http://dx.doi.org/10.1002/jnr.22034] [PMID: 19235898]
[119]
Voyle N, Baker D, Burnham SC, et al. AIBL research group. Blood protein markers of neocortical amyloid-β burden: a candidate study using SOMAscan technology. J Alzheimers Dis 2015; 46(4): 947-61.
[http://dx.doi.org/10.3233/JAD-150020] [PMID: 25881911]
[120]
Holzer P, Reichmann F, Farzi A. Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis. Neuropeptides 2012; 46(6): 261-74.
[http://dx.doi.org/10.1016/j.npep.2012.08.005] [PMID: 22979996]
[121]
Chiam JT, Dobson RJ, Kiddle SJ, Sattlecker M. Are blood-based protein biomarkers for Alzheimer’s disease also involved in other brain disorders? A systematic review. J Alzheimers Dis 2015; 43(1): 303-14.
[http://dx.doi.org/10.3233/JAD-140816] [PMID: 25096613]
[122]
Qiu WQ, Au R, Zhu H, et al. Positive association between plasma amylin and cognition in a homebound elderly population. J Alzheimers Dis 2014; 42(2): 555-63.
[http://dx.doi.org/10.3233/JAD-140210] [PMID: 24898659]
[123]
Burnham SC, Faux NG, Wilson W, et al. Alzheimer’s Disease Neuroimaging Initiative; Australian Imaging, Biomarkers and Lifestyle Study Research Group. A blood-based predictor for neocortical Aβ burden in Alzheimer’s disease: results from the AIBL study. Mol Psychiatry 2014; 19(4): 519-26.
[http://dx.doi.org/10.1038/mp.2013.40] [PMID: 23628985]
[124]
Schultz N, Janelidze S, Byman E, et al. Levels of islet amyloid polypeptide in cerebrospinal fluid and plasma from patients with Alzheimer’s disease. PLoS One 2019; 14(6) e0218561
[http://dx.doi.org/10.1371/journal.pone.0218561] [PMID: 31206565]
[125]
Marcello A, Wirths O, Schneider-Axmann T, Degerman-Gunnarsson M, Lannfelt L, Bayer TA. Reduced levels of IgM autoantibodies against N-truncated pyroglutamate Aβ in plasma of patients with Alzheimer’s disease. Neurobiol Aging 2011; 32(8): 1379-87.
[http://dx.doi.org/10.1016/j.neurobiolaging.2009.08.011] [PMID: 19781815]
[126]
Solé M, Esteban-Lopez M, Taltavull B, et al. Blood-brain barrier dysfunction underlying Alzheimer’s disease is induced by an SSAO/VAP-1-dependent cerebrovascular activation with enhanced Aβ deposition. Biochim Biophys Acta (BBA)-Mol Basis Dis 2019; 1865(9): 2189-202.
[127]
Solé M, Miñano-Molina AJ, Unzeta M. Cross-talk between Aβ and endothelial SSAO/VAP-1 accelerates vascular damage and Aβ aggregation related to CAA-AD. Neurobiol Aging 2015; 36(2): 762-75.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.09.030] [PMID: 25457560]
[128]
Ma Q-L, Teng E, Zuo X, et al. Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer’s disease. Neurobiol Dis 2018; 114: 120-8.
[http://dx.doi.org/10.1016/j.nbd.2018.02.014] [PMID: 29501530]
[129]
Figueiro-Silva J, Gruart A, Clayton KB, et al. Neuronal pentraxin 1 negatively regulates excitatory synapse density and synaptic plasticity. J Neurosci 2015; 35(14): 5504-21.
[http://dx.doi.org/10.1523/JNEUROSCI.2548-14.2015] [PMID: 25855168]
[130]
Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol 2018; 14: 450-64.
[http://dx.doi.org/10.1016/j.redox.2017.10.014] [PMID: 29080524]
[131]
Peña-Bautista C, Baquero M, Vento M, Cháfer-Pericás C. Free radicals in Alzheimer’s disease: Lipid peroxidation biomarkers. Clin Chim Acta 2019; 491: 85-90.
[http://dx.doi.org/10.1016/j.cca.2019.01.021]
[132]
Silvestrelli G, Lanari A, Parnetti L, Tomassoni D, Amenta F. Treatment of Alzheimer’s disease: from pharmacology to a better understanding of disease pathophysiology. Mech Ageing Dev 2006; 127(2): 148-57.
[http://dx.doi.org/10.1016/j.mad.2005.09.018] [PMID: 16278007]
[133]
Ayton S, Wang Y, Diouf I, et al. Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology. Mol Psychiatry 2019. Epub ahead of print
[http://dx.doi.org/10.1038/s41380-019-0375-7] [PMID: 30778133]
[134]
Lee P, Peng H, Gelbart T, Beutler E. The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulin-deficient hepatocytes. Proc Natl Acad Sci USA 2004; 101(25): 9263-5.
[http://dx.doi.org/10.1073/pnas.0403108101] [PMID: 15192150]
[135]
Chauhan V, Chauhan A. Oxidative stress in Alzheimer’s disease. Pathophysiology 2006; 13(3): 195-208.
[http://dx.doi.org/10.1016/j.pathophys.2006.05.004]
[136]
Nunomura A, Perry G, Aliev G, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001; 60(8): 759-67.
[http://dx.doi.org/10.1093/jnen/60.8.759] [PMID: 11487050]
[137]
Butterfield DA, Halliwell B. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat Rev Neurosci 2019; 20(3): 148-60.
[http://dx.doi.org/10.1038/s41583-019-0132-6] [PMID: 30737462]
[138]
Chen Z, Zhong C. Oxidative stress in Alzheimer’s disease. Neurosci Bull 2014; 30(2): 271-81.
[http://dx.doi.org/10.1007/s12264-013-1423-y] [PMID: 24664866]
[139]
Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014; 2014: 360438
[http://dx.doi.org/10.1155/2014/360438] [PMID: 24999379]
[140]
Ma E, Ingram KH, Milne GL, Garvey WT. F2-Isoprostanes reflect oxidative stress correlated with lean mass and bone density but not insulin resistance. J Endocr Soc 2017; 1(5): 436-48.
[http://dx.doi.org/10.1210/js.2017-00006] [PMID: 29264499]
[141]
Mohamed W, Sayeed S, Saxena A, Oothuman P. Oxidative stress status and neuroprotection of tocotrienols in chronic cerebral hypoperfusion-induced neurodegeneration rat animal model. International J Nutrit, Pharm. Neurol Dis 2018; 8(2): 47-52.
[142]
Irizarry MC, Yao Y, Hyman BT, Growdon JH, Praticò D. Plasma F2A isoprostane levels in Alzheimer’s and Parkinson’s disease. Neurodegener Dis 2007; 4(6): 403-5.
[http://dx.doi.org/10.1159/000107699] [PMID: 17934322]
[143]
Grotto D, Maria LS, Valentini J, et al. Importance of the lipid peroxidation biomarkers and methodological aspects for malondialdehyde quantification. Quim Nova 2009; 32(1): 169-74.
[http://dx.doi.org/10.1590/S0100-40422009000100032]
[144]
Arnett D, Quillin A, Geldenhuys WJ, Menze MA, Konkle M. 4-hydroxynonenal and 4-oxononenal differentially bind to the redox sensor mitoNEET. Chem Res Toxicol 2019; 32(6): 977-81.
[http://dx.doi.org/10.1021/acs.chemrestox.9b00166] [PMID: 31117349]
[145]
Selley ML, Close DR, Stern SE. The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer’s disease. Neurobiol Aging 2002; 23(3): 383-8.
[http://dx.doi.org/10.1016/S0197-4580(01)00327-X] [PMID: 11959400]
[146]
McGrath LT, McGleenon BM, Brennan S, McColl D, McILroy S, Passmore AP. Increased oxidative stress in Alzheimer’s disease as assessed with 4-hydroxynonenal but not malondialdehyde. QJM 2001; 94(9): 485-90.
[http://dx.doi.org/10.1093/qjmed/94.9.485] [PMID: 11528012]
[147]
Calabrese V, Sultana R, Scapagnini G, et al. Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer’s disease. Antioxid Redox Signal 2006; 8(11-12): 1975-86.
[http://dx.doi.org/10.1089/ars.2006.8.1975] [PMID: 17034343]
[148]
Torres LL, Quaglio NB, de Souza GT, et al. Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 2011; 26(1): 59-68.
[http://dx.doi.org/10.3233/JAD-2011-110284] [PMID: 21593563]
[149]
Puertas MC, Martínez-Martos JM, Cobo MP, Carrera MP, Mayas MD, Ramírez-Expósito MJ. Plasma oxidative stress parameters in men and women with early stage Alzheimer type dementia. Exp Gerontol 2012; 47(8): 625-30.
[http://dx.doi.org/10.1016/j.exger.2012.05.019] [PMID: 22664577]
[150]
Cristalli DO, Arnal N, Marra FA, de Alaniz MJT, Marra CA. Peripheral markers in neurodegenerative patients and their first-degree relatives. J Neurol Sci 2012; 314(1-2): 48-56.
[http://dx.doi.org/10.1016/j.jns.2011.11.001] [PMID: 22113180]
[151]
Galbusera C, Facheris M, Magni F, et al. Increased susceptibility to plasma lipid peroxidation in Alzheimer disease patients. Curr Alzheimer Res 2004; 1(2): 103-9.
[http://dx.doi.org/10.2174/1567205043332171] [PMID: 15975074]
[152]
Ceballos-Picot I, Merad-Boudia M, Nicole A, et al. CeballosPicot I.Peripheral antioxidant enzyme activities and selenium in elderly subjects and in dementia of Alzheimer’s type--place of the extracellular glutathione peroxidase. Free Radic Biol Med 1996; 20(4): 579-87.
[http://dx.doi.org/10.1016/0891-5849(95)02058-6] [PMID: 8904299]
[153]
Alomari E, Bruno S, Ronda L, Paredi G, Bettati S, Mozzarelli A. Protein carbonylation detection methods: A comparison. Data Brief 2018; 19: 2215-20.
[http://dx.doi.org/10.1016/j.dib.2018.06.088] [PMID: 30229098]
[154]
Greilberger J, Fuchs D, Leblhuber F, Greilberger M, Wintersteiger R, Tafeit E. Carbonyl proteins as a clinical marker in Alzheimer’s disease and its relation to tryptophan degradation and immune activation. Clin Lab 2010; 56(9-10): 441-8.
[PMID: 21086789]
[155]
Bermejo P, Martín-Aragón S, Benedí J, et al. Peripheral levels of glutathione and protein oxidation as markers in the development of Alzheimer’s disease from Mild Cognitive Impairment. Free Radic Res 2008; 42(2): 162-70.
[http://dx.doi.org/10.1080/10715760701861373] [PMID: 18297609]
[156]
Conrad CC, Marshall PL, Talent JM, Malakowsky CA, Choi J, Gracy RW. Oxidized proteins in Alzheimer’s plasma. Biochem Biophys Res Commun 2000; 275(2): 678-81.
[http://dx.doi.org/10.1006/bbrc.2000.3356] [PMID: 10964722]
[157]
Guo C, Ding P, Xie C, et al. Potential application of the oxidative nucleic acid damage biomarkers in detection of diseases. Oncotarget 2017; 8(43): 75767-77.
[http://dx.doi.org/10.18632/oncotarget.20801] [PMID: 29088908]
[158]
Mecocci P, Polidori MC, Cherubini A, et al. Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease. Arch Neurol 2002; 59(5): 794-8.
[http://dx.doi.org/10.1001/archneur.59.5.794] [PMID: 12020262]
[159]
Bonda DJ, Wang X, Perry G, Smith MA, Zhu X. Mitochondrial dynamics in Alzheimer’s disease: opportunities for future treatment strategies. Drugs Aging 2010; 27(3): 181-92.
[http://dx.doi.org/10.2165/11532140-000000000-00000] [PMID: 20210366]
[160]
Skoumalová A, Hort J. Blood markers of oxidative stress in Alzheimer’s disease. J Cell Mol Med 2012; 16(10): 2291-300.
[http://dx.doi.org/10.1111/j.1582-4934.2012.01585.x] [PMID: 22564475]
[161]
Berretta J, Morillon A. Pervasive transcription constitutes a new level of eukaryotic genome regulation. EMBO Rep 2009; 10(9): 973-82.
[http://dx.doi.org/10.1038/embor.2009.181] [PMID: 19680288]
[162]
Mattick JS. The central role of RNA in human development and cognition. FEBS Lett 2011; 585(11): 1600-16.
[http://dx.doi.org/10.1016/j.febslet.2011.05.001] [PMID: 21557942]
[163]
Uszczynska-Ratajczak B, Lagarde J, Frankish A, Guigó R, Johnson R. Towards a complete map of the human long non-coding RNA transcriptome. Nat Rev Genet 2018; 19(9): 535-48.
[http://dx.doi.org/10.1038/s41576-018-0017-y] [PMID: 29795125]
[164]
Adelman K, Egan E. Non-coding RNA: More uses for genomic junk. Nature 2017; 543(7644): 183-5.
[http://dx.doi.org/10.1038/543183a] [PMID: 28277509]
[165]
Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell 2013; 152(6): 1298-307.
[http://dx.doi.org/10.1016/j.cell.2013.02.012] [PMID: 23498938]
[166]
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75(5): 843-54.
[http://dx.doi.org/10.1016/0092-8674(93)90529-Y] [PMID: 8252621]
[167]
Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet 2015; 16(7): 421-33.
[http://dx.doi.org/10.1038/nrg3965] [PMID: 26077373]
[168]
Fineberg SK, Kosik KS, Davidson BL. MicroRNAs potentiate neural development. Neuron 2009; 64(3): 303-9.
[http://dx.doi.org/10.1016/j.neuron.2009.10.020] [PMID: 19914179]
[169]
Russo F, Di Bella S, Nigita G, et al. miRandola: extracellular circulating microRNAs database. PLoS One 2012; 7(10) e47786
[http://dx.doi.org/10.1371/journal.pone.0047786] [PMID: 23094086]
[170]
Kumar S, Reddy PH. Are circulating microRNAs peripheral biomarkers for Alzheimer’s disease? Biochim Biophys Acta 2016; 1862(9): 1617-27.
[http://dx.doi.org/10.1016/j.bbadis.2016.06.001] [PMID: 27264337]
[171]
Fransquet PD, Ryan J. Micro RNA as a potential blood-based epigenetic biomarker for Alzheimer’s disease. Clin Biochem 2018; 58: 5-14.
[http://dx.doi.org/10.1016/j.clinbiochem.2018.05.020] [PMID: 29885309]
[172]
Wang WX, Rajeev BW, Stromberg AJ, et al. The expression of microRNA miR-107 decreases early in Alzheimer’s disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. J Neurosci 2008; 28(5): 1213-23.
[http://dx.doi.org/10.1523/JNEUROSCI.5065-07.2008] [PMID: 18234899]
[173]
Nelson PT, Wang WX. MiR-107 is reduced in Alzheimer’s disease brain neocortex: validation study. J Alzheimers Dis 2010; 21(1): 75-9.
[http://dx.doi.org/10.3233/JAD-2010-091603] [PMID: 20413881]
[174]
Yao J, Hennessey T, Flynt A, Lai E, Beal MF, Lin MT. MicroRNA-related cofilin abnormality in Alzheimer’s disease. PLoS One 2010; 5(12) e15546
[http://dx.doi.org/10.1371/journal.pone.0015546] [PMID: 21179570]
[175]
Wang WX, Wilfred BR, Madathil SK, et al. miR-107 regulates granulin/progranulin with implications for traumatic brain injury and neurodegenerative disease. Am J Pathol 2010; 177(1): 334-45.
[http://dx.doi.org/10.2353/ajpath.2010.091202] [PMID: 20489155]
[176]
Siedlecki-Wullich D, Català-Solsona J, Fábregas C, et al. Altered microRNAs related to synaptic function as potential plasma biomarkers for Alzheimer’s disease. Alzheimers Res Ther 2019; 11(1): 46.
[http://dx.doi.org/10.1186/s13195-019-0501-4] [PMID: 31092279]
[177]
Nixon RA, Wegiel J, Kumar A, et al. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol 2005; 64(2): 113-22.
[http://dx.doi.org/10.1093/jnen/64.2.113] [PMID: 15751225]
[178]
Li Q, Wang Y, Peng W, et al. MicroRNA-101a regulates autophagy phenomenon via the MAPK pathway to modulate alzheimer’s-associated pathogenesis. Cell Transplant 2019; 28(8): 1076-84.
[http://dx.doi.org/10.1177/0963689719857085] [PMID: 31204500]
[179]
Nagaraj S, Laskowska-Kaszub K, Dębski KJ, et al. Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer’s disease patients from non-demented subjects. Oncotarget 2017; 8(10): 16122-43.
[http://dx.doi.org/10.18632/oncotarget.15109] [PMID: 28179587]
[180]
Olde Loohuis NF, Ba W, Stoerchel PH, et al. MicroRNA-137 controls AMPA-receptor-mediated transmission and mGluR-dependent LTD. Cell Rep 2015; 11(12): 1876-84.
[http://dx.doi.org/10.1016/j.celrep.2015.05.040] [PMID: 26095359]
[181]
Hu Z, Zhao J, Hu T, Luo Y, Zhu J, Li Z. miR-501-3p mediates the activity-dependent regulation of the expression of AMPA receptor subunit GluA1. J Cell Biol 2015; 208(7): 949-59.
[http://dx.doi.org/10.1083/jcb.201404092] [PMID: 25800054]
[182]
Hara N, Kikuchi M, Miyashita A, et al. Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer’s disease. Acta Neuropathol Commun 2017; 5(1): 10.
[http://dx.doi.org/10.1186/s40478-017-0414-z] [PMID: 28137310]
[183]
Geekiyanage H, Jicha GA, Nelson PT, Chan C. Blood serum miRNA: non-invasive biomarkers for Alzheimer’s disease. Exp Neurol 2012; 235(2): 491-6.
[http://dx.doi.org/10.1016/j.expneurol.2011.11.026] [PMID: 22155483]
[184]
Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA 2008; 105(36): 13421-6.
[http://dx.doi.org/10.1073/pnas.0801613105] [PMID: 18755897]
[185]
Bhatnagar S, Chertkow H, Schipper HM, et al. Increased microRNA-34c abundance in Alzheimer’s disease circulating blood plasma. Front Mol Neurosci 2014; 7: 2.
[http://dx.doi.org/10.3389/fnmol.2014.00002] [PMID: 24550773]
[186]
Swarbrick S, Wragg N, Ghosh S, Stolzing A. Systematic review of mirna as biomarkers in Alzheimer’s disease. Mol Neurobiol 2019; 56(9): 6156-67.
[http://dx.doi.org/10.1007/s12035-019-1500-y] [PMID: 30734227]
[187]
Manzine PR, Pelucchi S, Horst MA, et al. microRNA 221 Targets ADAM10 mRNA and is Downregulated in Alzheimer’s Disease. J Alzheimers Dis 2018; 61(1): 113-23.
[http://dx.doi.org/10.3233/JAD-170592] [PMID: 29036829]
[188]
Cortini F, Roma F, Villa C. Emerging roles of long non-coding RNAs in the pathogenesis of Alzheimer’s disease. Ageing Res Rev 2019; 50: 19-26.
[http://dx.doi.org/10.1016/j.arr.2019.01.001] [PMID: 30610928]
[189]
Feng L, Liao YT, He JC, et al. Plasma long non-coding RNA BACE1 as a novel biomarker for diagnosis of Alzheimer disease. BMC Neurol 2018; 18(1): 4.
[http://dx.doi.org/10.1186/s12883-017-1008-x] [PMID: 29316899]
[190]
Deng YY, Xiao L, Li W, et al. Plasma long noncoding RNA 51A as a stable biomarker of Alzheimer’s disease. Int J Clin Exp Pathol 2017; 10(4): 4694-9.
[191]
Andersen OM, Reiche J, Schmidt V, et al. Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci USA 2005; 102(38): 13461-6.
[http://dx.doi.org/10.1073/pnas.0503689102] [PMID: 16174740]
[192]
Deng Y, Xiao L, Li W, et al. Plasma long non-coding RNA 51A as a stable biomarker of Alzheimer’s disease. Clin Exp Pathol 2017; 10(4): 6.
[193]
Manzine PR, Barham EJ, Vale FA, Selistre-de-Araújo HS, Pavarini SC, Cominetti MR. Platelet a disintegrin and metallopeptidase 10 expression correlates with clock drawing test scores in Alzheimer’s disease. Int J Geriatr Psychiatry 2014; 29(4): 414-20.
[http://dx.doi.org/10.1002/gps.4020] [PMID: 23970375]
[194]
Manzine PR, Barham EJ, Vale FdeA, Selistre-de-Araújo HS, Iost Pavarini SC, Cominetti MR. Correlation between mini-mental state examination and platelet ADAM10 expression in Alzheimer’s disease. J Alzheimers Dis 2013; 36(2): 253-60.
[http://dx.doi.org/10.3233/JAD-130125] [PMID: 23579328]
[195]
Manzine PR, de França Bram JM, Barham EJ, et al. ADAM10 as a biomarker for Alzheimer’s disease: a study with Brazilian elderly. Dement Geriatr Cogn Disord 2013; 35(1-2): 58-66.
[http://dx.doi.org/10.1159/000345983] [PMID: 23306532]
[196]
Colciaghi F, Borroni B, Pastorino L, et al. [alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients. Mol Med 2002; 8(2): 67-74.
[http://dx.doi.org/10.1007/BF03402076] [PMID: 12080182]
[197]
Colciaghi F, Marcello E, Borroni B, et al. Platelet APP, ADAM 10 and BACE alterations in the early stages of Alzheimer disease. Neurology 2004; 62(3): 498-501.
[http://dx.doi.org/10.1212/01.WNL.0000106953.49802.9C] [PMID: 14872043]
[198]
Manzine PR, Marcello E, Borroni B, et al. ADAM10 gene expression in the blood cells of Alzheimer's disease patients and mild cognitive impairment subjectsBiomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals 2015; 20(3): 196-201.
[http://dx.doi.org/10.3109/1354750X.2015.1062554]
[199]
Schuck F, Wolf D, Fellgiebel A, Endres K. Increase of α-secretase ADAM10 in platelets along cognitively healthy aging. J Alzheimers Dis 2016; 50(3): 817-26.
[http://dx.doi.org/10.3233/JAD-150737] [PMID: 26757187]
[200]
Pellicanò M, Larbi A, Goldeck D, et al. Immune profiling of Alzheimer patients. J Neuroimmunol 2012; 242(1-2): 52-9.
[http://dx.doi.org/10.1016/j.jneuroim.2011.11.005] [PMID: 22153977]
[201]
Torres KC, Araújo Pereira P, Lima GS, et al. Increased frequency of T cells expressing IL-10 in Alzheimer disease but not in late-onset depression patients. Prog Neuropsychopharmacol Biol Psychiatry 2013; 47: 40-5.
[http://dx.doi.org/10.1016/j.pnpbp.2013.07.021] [PMID: 23954740]
[202]
Baldacci F, Daniele S, Piccarducci R, et al. Potential diagnostic value of red blood cells α-synuclein heteroaggregates in Alzheimer’s disease. Mol Neurobiol 2019; 56(9): 6451-9.
[http://dx.doi.org/10.1007/s12035-019-1531-4] [PMID: 30826968]
[203]
Vergallo A, Bun RS, Toschi N, et al. INSIGHT-preAD study group; Alzheimer Precision Medicine Initiative (APMI).Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer’s disease biomarkers. Alzheimers Dement 2018; 14(12): 1623-31.
[http://dx.doi.org/10.1016/j.jalz.2018.06.3053] [PMID: 30055132]
[204]
Tofaris GK, Buckley NJ. Convergent molecular defects underpin diverse neurodegenerative diseases. J Neurol Neurosurg Psychiatry 2018; 89(9): 962-9.
[http://dx.doi.org/10.1136/jnnp-2017-316988] [PMID: 29459380]