Harnessing peripheral DNA methylation differences in the Alzheimer's Disease Neuroimaging Initiative (ADNI) to reveal novel biomarkers of disease.

Clinical Epigenetics
Aparna VasanthakumarAlzheimer’s Disease Neuroimaging Initiative (ADNI)

Abstract

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease impacting an estimated 44 million adults worldwide. The causal pathology of AD (accumulation of amyloid-beta and tau), precedes hallmark symptoms of dementia by more than a decade, necessitating development of early diagnostic markers of disease onset, particularly for new drugs that aim to modify disease processes. To evaluate differentially methylated positions (DMPs) as novel blood-based biomarkers of AD, we used a subset of 653 individuals with peripheral blood (PB) samples in the Alzheimer's disease Neuroimaging Initiative (ADNI) consortium. The selected cohort of AD, mild cognitive impairment (MCI), and age-matched healthy controls (CN) all had imaging, genetics, transcriptomics, cerebrospinal protein markers, and comprehensive clinical records, providing a rich resource of concurrent multi-omics and phenotypic information on a well-phenotyped subset of ADNI participants. In this manuscript, we report cross-diagnosis differential peripheral DNA methylation in a cohort of AD, MCI, and age-matched CN individuals with longitudinal DNA methylation measurements. Epigenome-wide association studies (EWAS) were performed using a mixed model with repeated ...Continue Reading

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Citations

Dec 12, 2020·Free Radical Biology & Medicine·Fabio Coppedè
Nov 4, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Robert PhilibertMeeshanthini Dogan
Apr 13, 2021·Expert Opinion on Therapeutic Targets·Fabio Coppedè
Aug 13, 2021·Advanced Science·Siyu WeiYongshuai Jiang
Aug 15, 2021·Translational Neurodegeneration·Miao XuNan-Jie Xu
Oct 17, 2021·Clinical Epigenetics·Qingqin S LiUNKNOWN Alzheimer’s Disease Neuroimaging Initiative (ADNI)

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Methods Mentioned

BETA
chip
chips
genotyping

Software Mentioned

minfin
R
limma
methylumi
Genome Studio
Tissue Specific Expression Analysis ( TSEA )
estimateCellCounts
GTex Data
TSEA
Cham

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