Genetic modification of the relationship between phosphorylated tau and neurodegeneration.

Hohman TJ, Koran ME, Thornton-Wells TA, Alzheimer's Disease Neuroimaging Initiative
Alzheimers Dement. 2014 10 (6): 637-645.e1

PMID: 24656848 · PMCID: PMC4169762 · DOI:10.1016/j.jalz.2013.12.022

BACKGROUND - A subset of individuals present at autopsy with the pathologic features of Alzheimer's disease having never manifest the clinical symptoms. We sought to identify genetic factors that modify the relationship between phosphorylated tau (PTau) and dilation of the lateral inferior ventricles.

METHODS - We used data from 700 subjects enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). A genome-wide association study approach was used to identify PTau × single nucleotide polymorphism (SNP) interactions. Variance explained by these interactions was quantified using hierarchical linear regression.

RESULTS - Five SNP × PTau interactions passed a Bonferroni correction, one of which (rs4728029, POT1, 2.6% of variance) was consistent across ADNI-1 and ADNI-2/GO subjects. This interaction also showed a trend-level association with memory performance and levels of interleukin-6 receptor.

CONCLUSIONS - Our results suggest that rs4728029 modifies the relationship between PTau and both ventricular dilation and cognition, perhaps through an altered neuroinflammatory response.

Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

MeSH Terms (18)

Aged Aged, 80 and over Alzheimer Disease Apolipoproteins E Brain Cognition Disorders Cytokines Female Genome-Wide Association Study Genotype Humans Lateral Ventricles Linear Models Magnetic Resonance Imaging Male Nerve Degeneration Polymorphism, Single Nucleotide tau Proteins

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