AUTHOR=Liu Ying , Song Jing-Hui , Xu Wei , Hou Xiao-He , Li Jie-Qiong , Yu Jin-Tai , Tan Lan , Chi Song ,  and Alzheimer’s Disease Neuroimaging Initiative 

TITLE=The Associations of Cerebrospinal Fluid ApoE and Biomarkers of Alzheimer’s Disease: Exploring Interactions With Sex

JOURNAL=Frontiers in Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.633576

DOI=10.3389/fnins.2021.633576

ISSN=1662-453X

ABSTRACT=<sec><title>Background</title><p>Sex-related difference in Alzheimer’s disease (AD) has been proposed, and apolipoprotein E (ApoE) isoforms have been suggested to be involved in the pathogenesis of AD.</p></sec><sec><title>Objective</title><p>We aimed to explore whether cerebrospinal fluid (CSF) ApoE is associated with AD biomarkers and whether the associations are different (between sexes).</p></sec><sec><title>Methods</title><p>Data of 309 participants [92 with normal cognition, 148 with mild cognitive impairment (MCI), and 69 with AD dementia] from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were cross-sectionally evaluated with the multiple linear regression model and longitudinally with the multivariate linear mixed-effects model for the associations of CSF ApoE with AD biomarkers. Sex–ApoE interaction was used to estimate whether sex moderates the associations of CSF ApoE and AD biomarkers.</p></sec><sec><title>Results</title><p>Significant interactions between CSF ApoE and sex on AD biomarkers were observed [amyloid-β (Aβ): <italic>p</italic> = 0.0169 and phosphorylated-tau (p-tau): <italic>p</italic> = 0.0453]. In women, baseline CSF ApoE levels were significantly associated with baseline Aβ (<italic>p</italic> = 0.0135) and total-tau (t-tau) (<italic>p</italic> &lt; 0.0001) as well as longitudinal changes of the biomarkers (Aβ: <italic>p</italic> = 0.0104; t-tau: <italic>p</italic> = 0.0110). In men, baseline CSF ApoE levels were only correlated with baseline p-tau (<italic>p</italic> &lt; 0.0001) and t-tau (<italic>p</italic> &lt; 0.0001) and did not aggravate AD biomarkers longitudinally.</p></sec><sec><title>Conclusion</title><p>The associations between CSF ApoE and AD biomarkers were sex-specific. Elevated CSF ApoE was associated with longitudinal changes of AD biomarkers in women, which indicates that CSF ApoE might be involved in the pathogenesis of AD pathology in a sex-specific way.</p></sec>