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This study aimed to investigate the associations between ApoE4 with CSF A\u03b242, total tau (t-tau), phospho-tau181 (p-tau), and with the progression of decline in a large cohort of MCI subjects, both progressors to AD and other dementias, as well as non-progressors. We analyzed associations of CSF A\u03b242, p-tau and t-tau with ApoE4 allele frequency cross-sectionally and longitudinally over 3\u00a0years of follow-up in 195 individuals with a diagnosis of MCI-stable, MCI-AD converters and MCI progressing to other dementias from the German Dementia Competence Network. In the total sample, ApoE4 carriers had lower concentrations of CSF A\u03b242, and increased concentrations of t-tau and p-tau compared to non-carriers in a gene dose-dependent manner. Comparisons of these associations stratified by MCI-progression groups showed a significant influence of ApoE4 carriership and diagnostic group on all CSF biomarker levels. The effect of ApoE4 was present in MCI-stable individuals but not in the other groups, with ApoE4\u2009+\u2009carriers having decreased CSF A\u03b2 42 levels, and increased concentration of t-tau and p-tau. Longitudinally, individuals with abnormal t-tau and A\u03b242 had a more rapid progression of cognitive and clinical decline, independently of ApoE4 genotype. Overall, our results contribute to an emerging framework in which ApoE4 involves mechanisms associated with both CSF amyloid-\u03b2 burden and tau aggregation at specific time points in AD pathogenesis.<\/jats:p>","DOI":"10.1007\/s00702-022-02461-0","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T15:02:34Z","timestamp":1642777354000},"page":"477-486","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Don\u2019t forget about tau: the effects of ApoE4 genotype on Alzheimer\u2019s disease cerebrospinal fluid biomarkers in subjects with mild cognitive impairment\u2014data from the Dementia Competence Network"],"prefix":"10.1007","volume":"129","author":[{"given":"Gloria S.","family":"Benson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Hausner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Couturier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Lewczuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"H\u00fcll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Jahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Jessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Pantel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan J.","family":"Teipel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Schuchhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Wiltfang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kornhuber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1494-0813","authenticated-orcid":false,"given":"Lutz","family":"Fr\u00f6lich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"2461_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13195-020-00710-6","volume":"12","author":"MS Baek","year":"2020","unstructured":"Baek MS, Cho H, Lee HS et al (2020) Effect of APOE \u03b54 genotype on amyloid-\u03b2 and tau accumulation in Alzheimer\u2019s disease. 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