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IMR Press / JIN / Volume 20 / Issue 2 / DOI: 10.31083/j.jin2002027
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Open Access Original Research
Apolipoprotein E ε4 and ε3 alleles associate with cerebrospinal fluid tau and cognition in the presence of amyloid-$\beta{}$ in mild cognitive impairment but not in Alzheimer’s disease
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1 Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China
2 Department of Neurology, Chongqing University Central Hospital, 400014 Chongqing, China
3 The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC H3A 0G4, Canada
*Correspondence: zhanghuapro@hospital.cqmu.edu.cn (Hua Zhang)
§Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: https://ida.loni.usc.edu/login.jsp.
J. Integr. Neurosci. 2021, 20(2), 277–286; https://doi.org/10.31083/j.jin2002027
Submitted: 29 January 2021 | Revised: 16 February 2021 | Accepted: 29 April 2021 | Published: 30 June 2021
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

Apolipoprotein E is the most well-established genetic risk factor for Alzheimer’s disease. However, the associations of apolipoprotein E with tau pathology and cognition remain controversial. The research checks the hypothesis that the relationships between apolipoprotein E alleles and cerebrospinal fluid tau and cognition differ in persons with and without significant amyloid-$\beta$ deposition. We divided 1119 subjects into cognitively normal (n = 275), mild cognitive impairment (n = 629), and Alzheimer’s disease (n = 215), and these subjects were from the Alzheimer’s Disease Neuroimaging Initiative database. Linear regression models were used to compare the relationships of apolipoprotein E alleles with cerebrospinal fluid tau and cognition in persons with significant amyloid-$\beta$ deposition relative to individuals without significant amyloid-$\beta$ deposition. The associations of apolipoprotein E $\varepsilon$4 and $\varepsilon$3 with total tau (T-tau), phosphorylated tau (P-tau), and Alzheimer’s disease assessment scale was significantly substantial among participants with significant amyloid-$\beta$ deposition. Stratified analyses showed that apolipoprotein E $\varepsilon$4 related to increased concentrations of T-tau, P-tau, and Alzheimer’s disease assessment scale and apolipoprotein E $\varepsilon$3 associated with decreased concentrations of T-tau, P-tau, and Alzheimer’s disease assessment scale in mild cognitive impairment participants with significant amyloid-$\beta$ deposition, but not in Alzheimer’s disease. Our study shows that the presence of apolipoprotein E $\varepsilon$4 and $\varepsilon$3 alleles is related to tau pathology and cognitive impairment in the presence of amyloid-$\beta$ in mild cognitive impairment, but not in Alzheimer’s disease. This work indirectly provides additional evidence that apolipoprotein E and amyloid-$\beta$ may not have a role in modulating clinical Alzheimer’s disease, and apolipoprotein E $\varepsilon$3 may be supposed to be protective to mild cognitive impairment.

Keywords
Alzheimer's disease
Amyloid-β
Apolipoprotein E
Mild cognitive impairment
Tau
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