Apolipoprotein E epsilon 2 (APOE2), an allele of apolipoprotein E, is associated with milder Alzheimer’s disease pathology and less severe cognitive impairment when compared with APOE3 and 4 alleles, suggesting a relative neuroprotective effect of APOE2 in Alzheimer’s disease, investigators wrote in the Annals of Neurology.

“The main novel finding of this study is a significant negative direct effect of the APOE epsilon 2 allele on the Braak stage of [neurofibrillary tangles], suggesting a protective effect of the apolipoprotein E2 against NFT formation and spreading, whereas APOE epsilon 4 does not exhibit the opposite effect,” wrote the investigators, led by Dr. Alberto Serrano-Pozo of Massachusetts General Hospital in Boston.

Dr. Serrano-Pozo and his associates studied postmortem data from 2,987 subjects in the National Alzheimer’s Coordinating Center autopsy cohort, of whom 793 subjects met all the eligibility criteria. The researchers then built multivariable models to explore the relationship between the E2 and E4 alleles and Alzheimer’s disease neuropathology. The average last Mini Mental State Examination (MMSE) score of APOE2 carriers was 20.5, but the average MMSE score of APOE4 carriers was only 11.9 for one copy and 9.7 for two copies of the allele, with higher values indicating milder pathology.

Read the full article in Annals of Neurology (2015 [doi:10.1002/ana.24369]).

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