Role for ATXN1, ATXN2, and HTT intermediate repeats in frontotemporal dementia and Alzheimer's disease.

Alzheimer Disease / genetics Ataxin-1 / genetics Ataxin-2 / genetics C9orf72 Protein / genetics Cohort Studies Female Frontotemporal Dementia / genetics Gene Frequency Genotype Humans Huntingtin Protein / genetics Male Parkinson Disease / genetics Trinucleotide Repeat Expansion Trinucleotide Repeats

CAG repeats Intermediate alleles Neurodegeneration Tauopathies

Journal

Neurobiology of aging

ISSN: 1558-1497

Titre abrégé: Neurobiol Aging

Pays: United States

ID NLM: 8100437

Informations de publication

Date de publication:
03 2020

Historique:

received: 26 05 2019

revised: 03 10 2019

accepted: 26 10 2019

pubmed: 8 12 2019

medline: 15 9 2020

entrez: 8 12 2019

Statut: ppublish

Résumé

We analyzed the frequency of intermediate alleles (IAs) in the ATXN1, ATXN2, and HTT genes in several neurodegenerative diseases. The study included 1126 patients with Alzheimer's disease (AD), 440 patients with frontotemporal dementia (FTD), and 610 patients with Parkinson's disease. In all cohorts, we genotyped ATXN1 and ATXN2 CAG repeats. In addition, in the FTD cohort, we determined the number of HTT CAG repeats. The frequency of HTT IAs was higher in patients with FTD (6.9%) versus controls (2.9%) and in the C9orf72 expansion noncarriers (7.2%) versus controls (2.9%), although the difference was nonsignificant after correction for multiple testing. Compared with controls, progressive nonfluent aphasia (PNFA) groups showed a significantly higher frequency of HTT IAs (13.6% vs. 2.9% controls). For the ATXN2 gene, we observed an increase in IA frequency in AD cases (AD 4.1% vs. controls 1.8%) and in the behavioral FTD group (4.8% vs. 1.8%). For the ATXN1 gene, we found a significant increase of IAs in patients with PNFA (18.6%) versus controls (6.7%). In conclusion, our work suggests that the HTT and ATXN1 IAS may contribute to PNFA pathogenesis and point to a link between ATXN2 IAS and AD.

Identifiants

DOI: 10.1016/j.neurobiolaging.2019.10.017 PMID: 31810584

pubmed: 31810584

pii: S0197-4580(19)30381-1

doi: 10.1016/j.neurobiolaging.2019.10.017

pii:

doi:

Substances chimiques

ATXN1 protein, human 0

ATXN2 protein, human 0

Ataxin-1 0

Ataxin-2 0

C9orf72 Protein 0

C9orf72 protein, human 0

HTT protein, human 0

Huntingtin Protein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

139.e1-139.e7