New Genetic Approaches to AD: Lessons from APOE-TOMM40 Phylogenetics.

Journal Article (Journal Article;Review)

Clinical trials for Alzheimer's disease are now focusing on the earliest stages of the disease with the goal of delaying dementia onset. There is great utility in using genetic variants to identify individuals at high age-dependent risk when the goal is to begin treatment before the development of any cognitive symptoms. Genetic variants identified through large-scale genome-wide association studies have not substantially improved the accuracy provided by APOE genotype to identify people at high risk of late-onset Alzheimer's disease (LOAD). We describe novel approaches, focused on molecular phylogenetics, to finding genetic variants that predict age at LOAD onset with sufficient accuracy and precision to be useful. We highlight the discovery of a polymorphism in TOMM40 that, in addition to APOE, may improve risk prediction and review how TOMM40 genetic variants may impact the develop of LOAD independently from APOE. The analysis methods described in this review may be useful for other genetically complex human diseases.

Full Text

Duke Authors

Cited Authors

  • Lutz, MW; Crenshaw, D; Welsh-Bohmer, KA; Burns, DK; Roses, AD

Published Date

  • May 2016

Published In

Volume / Issue

  • 16 / 5

Start / End Page

  • 48 -

PubMed ID

  • 27039903

Electronic International Standard Serial Number (EISSN)

  • 1534-6293

Digital Object Identifier (DOI)

  • 10.1007/s11910-016-0643-8


  • eng

Conference Location

  • United States