TOMM40 intron 6 poly-T length, age at onset, and neuropathology of AD in individuals with APOE ε3/ε3.

Abstract

BACKGROUND:

This study investigates the association between TOMM40 poly-T length, age at onset, and neuropathology in individuals with Alzheimer's disease (AD) with the apolipoprotein E (APOE) ε3/ε3 allele.

METHODS:

Thirty-two presenilin 1 (PSEN1) mutation carriers with AD, 27 presenilin 2 (PSEN2) mutation carriers with AD, 59 participants with late-onset AD (LOAD), and 168 autopsied subjects from a community-based cohort were genotyped for TOMM40 intron 6 poly-T (rs10524523) length using short tandem repeat assays.

RESULTS:

Among AD individuals with PSEN2 mutations, the presence of a long poly-T was associated with an earlier age at onset, whereas there were no such associations for subjects with PSEN1 mutations or LOAD. In community-based participants, the presence of a long poly-T was associated with increased neuritic tangles and a greater likelihood of pathologically diagnosed AD.

CONCLUSION:

TOMM40 intron 6 poly-T length may explain some of the variation in age at onset in PSEN2 familial AD and may be associated with AD neuropathology in persons with APOE ε3/ε3.

• Authors: Ge Li, Lynn M Bekris, Lesley Leong, Ellen J Steinbart, Jane B Shofer, Paul K Crane, Eric B Larson, Elaine R Peskind, Thomas D Bird, Chang-En Yu
• Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association (Alzheimers Dement) Vol. 9 Issue 5 Pg. 554-61 (Sep 2013) ISSN: 1552-5279 [Electronic] United States
• PMID: 23183136 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 The Alzheimer's Association. All rights reserved.

Chemical References

• Apolipoprotein E3
• Membrane Transport Proteins
• Mitochondrial Precursor Protein Import Complex Proteins
• PSEN1 protein, human
• PSEN2 protein, human
• Presenilin-1
• Presenilin-2
• TOMM40 protein, human
• Poly T

Topics

• Adult
• Age of Onset
• Aged
• Aged, 80 and over
• Alzheimer Disease (genetics, pathology)
• Apolipoprotein E3 (genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Genotype
• Humans
• Introns
• Male
• Membrane Transport Proteins (genetics)
• Middle Aged
• Mitochondrial Precursor Protein Import Complex Proteins
• Mutation
• Poly T (genetics)
• Presenilin-1 (genetics)
• Presenilin-2 (genetics)