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APOE Allele Linked to Severity of Alzheimer’s Disease

Relatively rare APOEε2 allele associated with milder version of Alzheimer’s disease

FRIDAY, Feb. 6, 2015 (HealthDay News) — The APOEε2 allele may be associated with a milder clinical and pathological course of Alzheimer’s disease (AD), according to research published online Jan. 26 in the Annals of Neurology.

Alberto Serrano-Pozo, M.D., Ph.D., of Massachusetts General Hospital in Boston, and colleagues analyzed data for individuals from the National Alzheimer’s Coordinating Center autopsy cohort who had varying degrees of severity of disease across the clinical and pathological continuum of AD. The researchers examined the associations between APOE alleles and AD pathology and cognition.

The researchers found that, compared with APOEε3, APOEε2 is independently associated with lower Braak neurofibrillary tangle (NFT) stages and, possibly, fewer neuritic plaques; no direct effect on cerebral amyloid angiopathy (CAA) severity was observed. In contrast, APOEε4 is associated with more neuritic plaques and CAA, but it does not appear to have an independent effect on Braak NFT stage. According to unadjusted analyses, APOE genotypes are associated with markedly different results for cognitive performance (ε2>ε3>ε4). Mediation analysis indicates that these differences are mostly explained by differing effects on pathology.

“Even when adjusted for age of onset, symptom duration and other demographic variables, APOEε2 is associated with milder AD pathology and less severe antemortem cognitive impairment compared to APOEε3 and ε4 alleles, suggesting a relative neuroprotective effect of APOEε2 in AD,” the authors write.

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