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Effects of apolipoprotein E4 genotype on cerebro-cerebellar connectivity, brain atrophy, and cognition in patients with Alzheimer's disease

Published:September 22, 2022DOI:https://doi.org/10.1016/j.jns.2022.120435

      Highlights

      • AD patients with APOE4 have lower FC within the cerebro-cerebellar motor network.
      • AD patients with APOE4 show greater episodic memory impairment.
      • AD patients possessing ε4 allele show more reduced regional brain volume and more cortical thinning
      • FC changes between the cerebellar seeds and the MTG.R explains in episodic memory
      • APOE4 independently contributes to the disruptions of FC, brain morphometry and episodic memory performance in AD patients

      Abstract

      Introduction

      While several studies have substantially revealed the influence of the apolipoprotein E4 genotype (APOE4) on the vulnerability of Alzheimer's disease (AD), there are still far fewer studies investigating whether and how APOE4, in the absence of the amyloid-β (Aβ), alters regional brain atrophy, cerebro-cerebellar connectivity and cognitive performance in AD patients.

      Methods

      We employed MRI and neuropsychological data from 234 old adults with AD dementia, including 143 APOE4-positive (with ε2/ε4, ε3/ε4, or ε4/ε4 alleles) and 91 APOE4-negative (with ε2/ε2, ε2/ε3 or ε3/ε3), to investigate the cerebro-cerebellar connectivity in three cerebro-cerebellar brain networks: default mode network, motor network and affective-limbic network. Amyloid PET images were used to evaluate individual Aβ burdens, later used as covariates. Regional volumetric and cortical thickness measures were quantified in both the cerebellum and the cerebrum using the cerebellum segmentation algorithm and Freesurfer5.3, respectively.

      Results

      Our corrected functional connectivity (FC) results showed that APOE4 carriers (APOE4+) had lower FC within the cerebro-cerebellar motor network. In addition, significant group differences in regional cortical thickness were observed in the left Crus I, the right VIIB, left superior frontal, and right middle temporal gyri. Group differences in regional brain volumes were observed in the left lobule V and right parstriangularis. Furthermore, multiple linear regression analysis indicated that APOE4+ AD patients show greater episodic memory impairment.

      Conclusion

      Since amyloid-β, age, education, and gender were included as confounds in the statistical models, our findings suggest that APOE4 independently contributes to brain atrophy, disrupted FC, and associated memory declines in AD patients.

      Keywords

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