The effect of rare variants in TREM2 and PLD3 on longitudinal cognitive function in the Wisconsin Registry for Alzheimer's Prevention

摘要

Recent studies have found an association between functional variants inTREM2andPLD3and Alzheimer's disease (AD), but their effect on cognitive function is unknown. We examined the effect of these variants on cognitive function in 1449 participants from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of initially asymptomatic adults, aged 36–73 years at baseline, enriched for a parental history of AD. A comprehensive cognitive test battery was performed at up to 5 visits. A factor analysis resulted in 6 cognitive factors that were standardized intozscores (～N [0, 1]); the mean of thesezscores was also calculated. In linear mixed models adjusted for age, gender, practice effects, and self-reported race/ethnicity,PLD3V232M carriers had significantly lower meanzscores (p?= 0.02) and lower z scores for story recall (p?= 0.04), visual learning and memory (p?= 0.049), and speed and flexibility (p?= 0.02) than noncarriers.TREM2R47H carriers had marginally lowerzscores for speed and flexibility (p?= 0.06). In conclusion, a functional variant inPLD3was associated with significantly lower cognitive function in individuals carrying the variant than in noncarriers.