Nov 12, 2019

A/T/N polygenic risk score for cognitive decline in old age

BioRxiv : the Preprint Server for Biology
Annah M. MooreTimothy J Hohman

Abstract

We developed a novel polygenic risk score (PRS) based on the A/T/N (amyloid plaques (A), phosphorylated tau tangles (T), and neurodegeneration (N)) framework and compared a PRS based on clinical AD diagnosis to assess which was a better predictor of cognitive decline. We used summary statistics from genome wide association studies of cerebrospinal fluid amyloid β (A β 42) and phosphorylated tau (ptau181), left hippocampal volume (LHIPV), and late-onset AD dementia to calculate PRS for 1181 participants in the Alzheimers Disease Neuroimaging Initiative (ADNI). Individual PRS were averaged to generate a composite A/T/N PRS. We assessed the association of PRS with baseline and longitudinal cognitive composites of executive function and memory. The A/T/N PRS showed superior predictive performance on AD biomarkers and executive function decline compared to the clinical AD PRS. Results suggest that integration of genetic risk across AD biomarkers may improve prediction of disease progression.

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Mentioned in this Paper

Biological Markers
Study
Genome
Nerve Degeneration
Executive Function
Cerebrospinal Fluid
Alzheimer's Disease
Participant
Amyloid
Tau Proteins

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