AUTHOR=Shang Li , Dong Liling , Huang Xinying , Wang Tianyi , Mao Chenhui , Li Jie , Wang Jie , Liu Caiyan , Gao Jing 

TITLE=Association of APOE ε4/ε4 with fluid biomarkers in patients from the PUMCH dementia cohort

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=15

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1119070

DOI=10.3389/fnagi.2023.1119070

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>Apolipoprotein-E (<italic>APOE</italic>) ε4 is a major genetic risk factor for Alzheimer’s disease (AD). Current studies, which were mainly based on the clinical diagnosis rather than biomarkers, come to inconsistent conclusions regarding the associations of <italic>APOE ε4</italic> homozygotes (<italic>APOE ε4/ε4</italic>) and cerebrospinal fluid (CSF) biomarkers of AD. In addition, few studies have explored the associations of <italic>APOE ε4/ε4</italic> with plasma biomarkers. Therefore, we aimed to investigate the associations of <italic>APOE ε4/ε4</italic> with fluid biomarkers in dementia and biomarker-diagnosed AD.</p></sec><sec><title>Methods</title><p>A total of 297 patients were enrolled. They were classified into Alzheimer’s continuum, AD, and non-AD, according to CSF biomarkers and/or β amyloid PET results. AD was a subgroup of the AD continuum. Plasma Amyloid β (Aβ) 40, Aβ42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and phosphorylated tau (P-tau)181 were quantified in 144 of the total population using an ultra-sensitive Simoa technology. We analyzed the associations of <italic>APOE ε4/ε4</italic> on CSF and plasma biomarkers in dementia and biomarker diagnosed AD.</p></sec><sec><title>Results</title><p>Based on the biomarker diagnostic criteria, 169 participants were diagnosed with Alzheimer’s continuum and 128 individuals with non-AD, and among the former, 120 patients with AD. The <italic>APOE ε4/ε4</italic> frequencies were 11.8% (20/169), 14.2% (17/120), and 0.8% (1/128) in Alzheimer’s continuum, AD and non-AD, respectively. Only CSF Aβ42 was shown to be decreased in <italic>APOE ε4/ε4</italic> carriers than in non-carriers for patients with AD (<italic>p</italic> = 0.024). Furthermore, we did not find any associations of <italic>APOE ε4</italic> with plasma biomarkers of AD and non-AD. Interestingly, we found that in non-AD patients, <italic>APOE ε4</italic> carriers had lower CSF Aβ42 (<italic>p</italic> = 0.018) and higher T-tau/Aβ42 ratios (<italic>p</italic> &lt; 0.001) and P-tau181/Aβ42 ratios (<italic>p</italic> = 0.002) than non-carriers.</p></sec><sec><title>Conclusion</title><p>Our data confirmed that of the three groups (AD continuum, AD, and non-AD), those with AD had the highest frequency of <italic>APOE ɛ4/ɛ4</italic> genotypes. The <italic>APOE ɛ4/ɛ4</italic> was associated with CSF levels of Aβ42 but not tau for AD and non-AD, suggesting that <italic>APOE ɛ4/ɛ4</italic> affected the Aβ metabolism of both. No associations between <italic>APOE ε4/ɛ4</italic> and plasma biomarkers of AD and non-AD were found.</p></sec>