Dataset Information

Polygenic risk for Alzheimer's disease is associated with neuroaxonal damage before onset of clinical symptoms.

ABSTRACT:

Introduction

Establishing valid diagnostic strategies is a precondition for successful therapeutic intervention in Alzheimer's disease (AD).

Methods

One hundred forty-four healthy 75-year-old participants from the Vienna-Transdanube-Aging longitudinal cohort study were tested for neuroaxonal damage by single molecular array (Simoa) plasma neurofilament light chain (NfL) levels at baseline, 30, 60, and 90 months, and onset of AD dementia. Individual risk for sporadic AD was estimated by continuous shrinkage polygenic risk score (PRS-CS, genome-wide association study).

Results

Nineteen participants developed AD after a median of 60 months (interquartile range 30). In participants with AD, baseline NfL plasma levels correlated with PRS-CS (r = 0.75, p < 0.001; difference to controls: Fisher's r-to-z: z = 3.89, p < 0.001). PRS-CS combined with baseline plasma NfL predicted onset of AD (p < 0.01).

Discussion

Our data suggest that polygenic risk for AD and plasma NfL closely interact years before onset of clinical symptoms. Peripheral NfL may serve as a diagnostic measure supporting early therapeutic intervention and secondary prevention in AD.

SUBMITTER: Kagerer SM

PROVIDER: S-EPMC10776830 | biostudies-literature | 2024 Jan-Mar

REPOSITORIES: biostudies-literature

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Publications

Polygenic risk for Alzheimer's disease is associated with neuroaxonal damage before onset of clinical symptoms.

Kagerer Sonja M SM Awasthi Swapnil S Ripke Stephan S Maceski Aleksandra A Benkert Pascal P Fall Aïda B AB Riederer Peter P Fischer Peter P Walitza Susanne S Grünblatt Edna E Kuhle Jens J Unschuld Paul G PG

Alzheimer's & dementia (Amsterdam, Netherlands) 20240109 1

<h4>Introduction</h4>Establishing valid diagnostic strategies is a precondition for successful therapeutic intervention in Alzheimer's disease (AD).<h4>Methods</h4>One hundred forty-four healthy 75-year-old participants from the Vienna-Transdanube-Aging longitudinal cohort study were tested for neuroaxonal damage by single molecular array (Simoa) plasma neurofilament light chain (NfL) levels at baseline, 30, 60, and 90 months, and onset of AD dementia. Individual risk for sporadic AD was estimat ...[more]

PMID: 38213949

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Project description:Background and aimsGenetic risk can influence disease progression. We measured the impact of genetic risk for substance use disorders (SUDs) on substance use onset and progression of symptoms.Design, setting, participantsUsing findings from genome-wide association studies (GWASs) of alcohol use disorder (AUD), opioid use disorder (OUD) and smoking trajectory (SMK) as discovery samples, we calculated polygenic risk scores (PRSs) in a deeply phenotyped independent target sample. Participants in the target sample were recruited from 2000 to 2020 from US inpatient or outpatient settings or through advertisements and comprised 5692 European-ancestry individuals (EUR) (56.2% male) and 4918 African-ancestry individuals (AFR) (54.9% male).MeasurementsThis study measured age of first substance use, regular use, reported problems and dependence diagnosis and progression from regular use to onset of problems and dependence for alcohol, opioids and smoking. We examined the contribution of PRS to each milestone and progression measure.FindingsEUR and males reported an earlier onset and shorter progression times than AFR and females, respectively. Among EUR, higher AUD PRS predicted earlier onset and more rapid progression to alcohol-related milestones (P < 0.001). Although the AUD PRS was a stronger moderator of problem onset among females (P = 0.017), it was more predictive of the progression to problems among males (P = 0.005). OUD and SMK PRS in EUR also predicted earlier onset of the respective milestones (P < 0.001). Among AFR, where power is lower due to the smaller discovery sample, AUD PRS predicted age of regular alcohol use (P = 0.039) and dependence (P = 0.001) and progression from regular use to diagnosis (P = 0.045), while SMK PRS predicted earlier age of initiation (P = 0.036).ConclusionsGenetic risk for SUDs appears to predict substance use milestones and symptom progression among European-ancestry individuals and, to a lesser extent, African-ancestry individuals.

Dataset Information

Polygenic risk for Alzheimer's disease is associated with neuroaxonal damage before onset of clinical symptoms.

Introduction

Methods

Results

Discussion

Publications

Polygenic risk for Alzheimer's disease is associated with neuroaxonal damage before onset of clinical symptoms.

Similar Datasets

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