%0 Journal Article %J J Alzheimers Dis %D 2019 %T Education Moderates the Relation Between APOE ɛ4 and Memory in Nondemented Non-Hispanic Black Older Adults. %A Vonk, Jet M J %A Rentería, Miguel Arce %A Medina, Valerie M %A Pericak-Vance, Margaret A %A Byrd, Goldie S %A Haines, Jonathan %A Brickman, Adam M %A Manly, Jennifer J %X

BACKGROUND: The APOEɛ4 allele is a well-known risk factor for Alzheimer's disease (AD). Previous research argues that higher education helps to preserve cognition in older adults with AD pathology because of its key role in cognitive reserve and resilience.

OBJECTIVE: To test if higher educational level buffers the effect of APOEɛ4 on cognition among older non-Hispanic Blacks.

METHODS: Participants were 849 non-demented older non-Hispanic Blacks (38.3% APOEɛ4+), who underwent a comprehensive neuropsychological evaluation. Multiple linear regression models tested the relationship between APOEɛ4 status and twelve cognitive measures with education (up to high school and beyond high school) as a moderator.

RESULTS: Education buffered the effects of the APOEɛ4 allele, such that there was no impact of APOEɛ4 status on word-list memory retention and working memory among participants with more than a high school degree. This pattern was not observed for ten other cognitive measures of verbal and visual episodic memory, semantic memory, executive function, and processing speed-although a similar trend was observed for switching ability in executive functioning. The buffering effect of education was stronger among women than men.

CONCLUSION: Our findings suggest that genetic effects on late-life cognition may be modified by environmental factors such as educational attainment. These results are consistent with the framework of cognitive reserve such that engaging in cognitively enriching activities and acquiring skills and knowledge with more years of education may increase the capacity to maintain cognitive function despite high genetic risk for impairment.

%B J Alzheimers Dis %V 72 %P 495-506 %8 2019 Nov 12 %G eng %N 2 %R 10.3233/JAD-190415 %0 Journal Article %J J Alzheimers Dis %D 2017 %T A Common Variant of IL-6R is Associated with Elevated IL-6 Pathway Activity in Alzheimer's Disease Brains. %A Haddick, Patrick C G %A Larson, Jessica L %A Rathore, Nisha %A Bhangale, Tushar R %A Phung, Qui T %A Srinivasan, Karpagam %A Hansen, David V %A Lill, Jennie R %A Pericak-Vance, Margaret A %A Haines, Jonathan %A Farrer, Lindsay A %A Kauwe, John S %A Schellenberg, Gerard D %A Cruchaga, Carlos %A Goate, Alison M %A Behrens, Timothy W %A Watts, Ryan J %A Graham, Robert R %A Kaminker, Joshua S %A van der Brug, Marcel %X

The common p.D358A variant (rs2228145) in IL-6R is associated with risk for multiple diseases and with increased levels of soluble IL-6R in the periphery and central nervous system (CNS). Here, we show that the p.D358A allele leads to increased proteolysis of membrane bound IL-6R and demonstrate that IL-6R peptides with A358 are more susceptible to cleavage by ADAM10 and ADAM17. IL-6 responsive genes were identified in primary astrocytes and microglia and an IL-6 gene signature was increased in the CNS of late onset Alzheimer's disease subjects in an IL6R allele dependent manner. We conducted a screen to identify variants associated with the age of onset of Alzheimer's disease in APOE ɛ4 carriers. Across five datasets, p.D358A had a meta P = 3 ×10-4 and an odds ratio = 1.3, 95% confidence interval 1.12 -1.48. Our study suggests that a common coding region variant of the IL-6 receptor results in neuroinflammatory changes that may influence the age of onset of Alzheimer's disease in APOE ɛ4 carriers.

%B J Alzheimers Dis %V 56 %P 1037-1054 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28106546?dopt=Abstract %R 10.3233/JAD-160524