Author(s): Meng Zhou, Tianwen Huang, Nicole Collins, Jing Zhang, Hui Shen, Xiaoman Dai, Naian Xiao, Xilin Wu, Zhen Wei, Jason York, Lanyan Lin, Yuangui Zhu, Mary Jo LaDu and Xiaochun Chen
Page: [1048 - 1055] Pages: 8
* (Excluding Mailing and Handling)
APOE4 is the greatest genetic risk factor for Alzheimer’s disease (AD), particularly associated with increased levels of amyloid-β (Aβ) and amyloid deposition. However, it remains unclear whether APOE4 is associated with greater tau phosphorylation and neurofibrillary tangle formation, a hallmark of AD leading to structural disruption of the neuronal cytoskeleton. The current study used 3 and 7 month old EFAD mice, which express human APOE and over-express specifically human Aβ42 via 5 familial-AD (FAD) mutations, to investigate APOE genotype-specific effects on site-specific tau phosphorylation. The results reveal that AD-like site-specific tau phosphorylation was increased in E4FAD mice, accompanied by disrupted cortical neuronal morphology, compared to E3FAD mice. Further analysis demonstrated that the levels of CDK5, its regulatory subunits (p35 and p25) and calpain (including calpain1 and calpain2), but not GSK3β, were significantly increased in E4FAD mice compared to E3FAD mice. These results suggest that the APOE4 genotype contributes to increased site-specific tau phosphorylation via activation of the calpain-CDK5 signaling pathway.
Keywords: Apolipoprotein E, amyloid beta, Alzheimer’s disease, calpain-CDK5, EFAD mice, phosphorylation, tau.
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CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51704007 and j.to_ip >=51704007 )) and ((j.from_date <= 1737598904 and j.to_date >= 1737598904 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 75024)
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select * from `article` where `first_page` < '1048' and is_uploaded = 1 and issue_id = 7175 order by cast(first_page as SIGNED) desc limit 1
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select * from `article` where `last_page` > '1055' and is_uploaded = 1 and issue_id = 7175 order by cast(first_page as SIGNED) asc limit 1
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select `language_id` from `multilanguage` where `short_code` = 'en'
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select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
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select `id` from `multilanguage_article` where `article_id` = 75024 limit 1
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select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 66 and `b`.`banner_from_date` <= 1737598904 and `b`.`banner_to_date` >= 1737598904 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
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select count(*) as aggregate from `uc_cart_products` where cart_id='5a93acad788e41143f431df3f08f3992'
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200
[]
[]
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