APOE ε 4 and resting‐state functional connectivity in racially/ethnically diverse older adults

Abstract

Introduction Numerous neuroimaging studies demonstrated an association between the apolipoprotein E (APOE) ε 4 allele and resting‐state functional connectivity (rsFC) of regions within the default mode network (DMN), both in healthy populations and patients with AD. It remains unclear whether the APOE ε 4 allele differentially affects the brain's functional network architecture across race/ethnicity. Methods We investigated rsFC within DMN subsystems in 170 APOE ε 4 carriers compared to 387 APOE ε 4 non‐carriers across three major racial/ethnic groups, including non‐Hispanic Whites (n = 166), non‐Hispanic Blacks (n = 185), and Hispanics (n = 206) from the Washington Heights‐Inwood Columbia Aging Project. Results Compared to APOE ε 4 non‐carriers, APOE ε 4 carriers had lower rsFC in temporal DMN, but only in non‐Hispanic Whites. Non‐Hispanic Black and Hispanic APOE ε 4 carriers had slightly higher or similar rsFC compared with non‐Hispanic White APOE ε 4 non‐carriers. Discussion These findings suggest that APOE ε 4 modulates DMN rsFC differently in non‐Hispanic Whites compared with non‐Hispanic Blacks and Hispanics.

The link between static and dynamic brain functional network connectivity and genetic risk of Alzheimer’s disease

“…However, no significant difference between the two groups was observed by looking at OCR. While previous studies only analyzed sFNC (Axelrud et al, 2019;Chiesa et al, 2017;McKenna et al, 2016;Turney et al, 2020), the results reported above demonstrated the importance of examining both sFNC and dFNC data to differentiate individuals with different AD risks.…”

“…CC-BY-NC-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is The copyright holder for this preprint this version posted March 29, 2021. ; https://doi.org/10.1101/2021.03.27.437354 doi: bioRxiv preprint temporal default mode network (DMN) functional connectivity than those without ɛ4 (Turney et al, 2020). Another study showed an increase in functional connectivity between the hippocampus and prefrontal/parietal/temporal cortex in healthy individuals carrying ɛ4 (Zheng et al, 2018).…”

“…Previous studies explored the link between AD's genetic risk and static functional network connectivity or sFNC (Axelrud et al, 2019;Chiesa et al, 2017;McKenna et al, 2016;Turney et al, 2020). For example, a recent study found that individuals carrying ɛ4 have lower temporal default mode network (DMN) functional connectivity than those without ɛ4 (Turney et al, 2020).…”

“…Previous studies explored the link between AD's genetic risk and static functional network connectivity or sFNC (Axelrud et al, 2019;Chiesa et al, 2017;McKenna et al, 2016;Turney et al, 2020). For example, a recent study found that individuals carrying ɛ4 have lower temporal default mode network (DMN) functional connectivity than those without ɛ4 (Turney et al, 2020). Another study showed an increase in functional connectivity between the hippocampus and prefrontal/parietal/temporal cortex in healthy individuals carrying ɛ4 (Zheng et al, 2018).…”

Effect ofAPOEε4 allele on levels of apolipoproteins E, J, and D, and redox signature in circulating extracellular vesicles from cognitively impaired with no dementia participants converted to Alzheimer's disease

“…Apolipoprotein E ( APOE ) ε4 allele is the most important predictor factor, besides age, of subsequent progression to AD 3 . Remarkable ethnicity‐specific effects of APOE ε4 on AD risk were reported and it is suggested that APOE ε4‐related cognitive impairment is racial‐dependent 4,5 . The apoE protein, mainly produced by liver parenchymal cells, is fundamental to maintain lipoproteins’ structural integrity and to promote their solubilization in blood circulation 6 .…”