Towards precision medicine in Alzheimer's disease: deciphering genetic data to establish informative biomarkers.

Published

Journal Article

INTRODUCTION: Developing biomarker tools for identification of individuals at high-risk for late-onset Alzheimer's disease (LOAD) is important for prognosis and early treatment. This review focuses on genetic factors and their potential role for precision medicine in LOAD. AREAS COVERED: APOEe4 is the strongest genetic risk factor for non-Mendelian LOAD, and the APOE-linkage disequilibrium (LD) region has produced the most significant association signal in multi-center genome-wide-association-studies (GWAS). Consideration of extended haplotypes in the APOE-LD region and specifically, non-coding variants in putative enhancer elements, such as the TOMM40-polyT, in-addition to the coding variants that comprise the APOE-genotypes, may be useful for predicting subjects at high-risk of developing LOAD and estimating age-of-onset of early disease-stage symptoms. A genetic-biomarker based on APOE-TOMM40-polyT haplotypes, and age is currently applied in a clinical trial for prevention/delay of LOAD onset. Additionally, we discuss LOAD-GWAS discoveries and the development of new genetic risk scores based on LOAD-GWAS findings other than the APOE-LD region. EXPERT COMMENTARY: Deciphering the precise causal genetic-variants within LOAD-GWAS regions will advance the development of genetic-biomarkers to complement and refine the APOE-LD region based prediction model. Collectively, the genetic-biomarkers will be translational for early diagnosis and enrichment of clinical trials with subjects at high-risk.

Full Text

Duke Authors

Cited Authors

  • Chiba-Falek, O; Lutz, MW

Published Date

  • 2017

Published In

Volume / Issue

  • 2 / 1

Start / End Page

  • 47 - 55

PubMed ID

  • 28944295

Pubmed Central ID

  • 28944295

International Standard Serial Number (ISSN)

  • 2380-8993

Digital Object Identifier (DOI)

  • 10.1080/23808993.2017.1286227

Language

  • eng

Conference Location

  • England