AUTHOR=Lai Ying-Liang Larry , Chen Kuan , Lee Tzu-Wei , Tso Chao-Wei , Lin Hui-Hsien , Kuo Li-Wei , Chen Cheng-Yu , Liu Hua-Shan 

TITLE=The Effect of the APOE-ε4 Allele on the Cholinergic Circuitry for Subjects With Different Levels of Cognitive Impairment

JOURNAL=Frontiers in Neurology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.651388

DOI=10.3389/fneur.2021.651388

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> Cholinergic deficiency has been suggested to associate with the abnormal accumulation of Aβ and tau for patients with Alzheimer's disease (AD). However, no studies have investigated the effect of <italic>APOE</italic>-ε4 and group differences in modulating the cholinergic basal forebrain–amygdala network for subjects with different levels of cognitive impairment. We evaluated the effect of <italic>APOE</italic>-ε4 on the cholinergic structural association and the neurocognitive performance for subjects with different levels of cognitive impairment.</p><p><bold>Methods:</bold> We used the structural brain magnetic resonance imaging scans from the Alzheimer's Disease Neuroimaging Initiative dataset. The study included cognitively normal (CN, <italic>n</italic> = 167) subjects and subjects with significant memory concern (SMC, <italic>n</italic> = 96), early mild cognitive impairment (EMCI, <italic>n</italic> = 146), late cognitive impairment (LMCI, <italic>n</italic> = 138), and AD (<italic>n</italic> = 121). Subjects were further categorized according to the <italic>APOE</italic>-ε4 allele carrier status. The main effects of <italic>APOE</italic>-ε4 and group difference on the brain volumetric measurements were assessed. Regression analyses were conducted to evaluate the associations among cholinergic structural changes, <italic>APOE</italic>-ε4 status, and cognitive performance.</p><p><bold>Results:</bold> We found that <italic>APOE</italic>-ε4 carriers in the disease group showed higher brain atrophy than non-carriers in the cholinergic pathway, while there is no difference between carriers and non-carriers in the CN group. <italic>APOE</italic>-ε4 allele carriers in the disease groups also exhibited a stronger cholinergic structural correlation than non-carriers did, while there is no difference between the carriers and non-carriers in the CN subjects. Disease subjects exhibited a stronger structural correlation in the cholinergic pathway than CN subjects did. Moreover, <italic>APOE-</italic>ε4 allele carriers in the disease group exhibited a stronger correlation between the volumetric changes and cognitive performance than non-carriers did, while there is no difference between carriers and non-carriers in CN subjects. Disease subjects exhibited a stronger correlation between the volumetric changes and cognitive performance than CN subjects did.</p><p><bold>Conclusion:</bold> Our results confirmed the effect of <italic>APOE-</italic>ε4 on and group differences in the associations with the cholinergic structural changes that may reflect impaired brain function underlying neurocognitive degeneration in AD.</p>