The protective PLCG2 variants delay Alzheimer’s disease onset age in APOE ε 4 carriers
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INTRODUCTION
We investigated the impact of protective PLCG2 -P522R and PLCG2 -3’UTR variants, and the TREM2 -R62H risk variant on Alzheimer’s disease (AD) onset age in relation to APOE ε4 status. Plasma-based biomarkers of the different variants were also explored.
METHODS
Kaplan-Meier and survival analyses were performed using FinnGen genotype and clinical endpoint data to assess the onset ages of AD, anxiety, and type 2 diabetes. Plasma biomarkers related to metabolism and inflammation were analyzed in 145 FINGER cohort participants.
RESULTS
PLCG2 -P522R and PLCG2 -3’UTR variants delayed AD onset, including among APOE ε 4 carriers. PLCG2 -P522R carriers showed elevated plasma ghrelin levels. TREM2 -R62H variant associated with an earlier onset of AD in APOE ε 4 carriers.
DISCUSSION
Protective PLCG2 variants may mitigate APOE ε 4-mediated risk of AD, which coincide with increased plasma levels of ghrelin. These findings highlight the further need to explore biomarkers and mechanisms associated with the protective variants in relation to APOE ε 4.
