The Effect of Rare Variants in TREM2 and PLD3 on Longitudinal Cognitive Function in the Wisconsin Registry for Alzheimer's Prevention

Authors

Corinne D. Engelman, University of Wisconsin School of Medicine and Public Health
Burcu F. Darst, University of Wisconsin School of Medicine and Public Health
Murat Bilgel, National Institute on AgingFollow
Eva Vasiljevic, University of Wisconsin School of Medicine and Public Health
Rebecca L. Koscik, University of Wisconsin School of Medicine and Public HealthFollow
Bruno M. Jedynak, Portland State UniversityFollow
Sterling C. Johnson, University of Wisconsin School of Medicine and Public HealthFollow

Document Type

Post-Print

Publication Date

12-29-2017

Subjects

Alzheimer's disease -- Genetics, Nervous system -- Diseases -- Genetic aspects, Alzheimer's disease -- Longitudinal studies, Cognition disorders

Abstract

Recent studies have found an association between functional variants in TREM2 and PLD3 and 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 into z scores (∼N [0, 1]); the mean of these z scores was also calculated. In linear mixed models adjusted for age, gender, practice effects, and self-reported race/ethnicity, PLD3 V232M carriers had significantly lower mean z scores (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. TREM2 R47H carriers had marginally lower z scores for speed and flexibility (p = 0.06). In conclusion, a functional variant in PLD3 was associated with significantly lower cognitive function in individuals carrying the variant than in noncarriers.

Description

© 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

NOTICE: this is the author’s version of a work that was accepted for publication in Neurobiology of Aging. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neurobiology of Aging, (December 2017). https://doi.org/10.1016/j.neurobiolaging.2017.12.025

DOI

10.1016/j.neurobiolaging.2017.12.025

Persistent Identifier

http://archives.pdx.edu/ds/psu/24660

Citation Details

Engelman, Corinne D.; Darst, Burcu F.; Bilgel, Murat; Vasiljevic, Eva; Koscik, Rebecca L.; Jedynak, Bruno M.; and Johnson, Sterling C., "The Effect of Rare Variants in TREM2 and PLD3 on Longitudinal Cognitive Function in the Wisconsin Registry for Alzheimer's Prevention" (2017). Mathematics and Statistics Faculty Publications and Presentations. 205.
http://archives.pdx.edu/ds/psu/24660