Exploring first-degree family history in a cohort of Portuguese Alzheimer's disease patients: population evidence for X-chromosome linked and recessive inheritance of risk factors.
Alzheimer
Consanguinity
Family
Homozygosity
X-chromosome
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
05 Sep 2024
05 Sep 2024
Historique:
received:
22
07
2024
accepted:
26
08
2024
revised:
11
08
2024
medline:
5
9
2024
pubmed:
5
9
2024
entrez:
5
9
2024
Statut:
aheadofprint
Résumé
Alzheimer's disease (AD) heritability is estimated to be around 70-80%. Yet, much of it remains to be explained. Studying transmission patterns may help in understanding other factors contributing to the development of AD. In this study, we aimed to search for evidence of autosomal recessive or X- and Y-linked inheritance of risk factors in a large cohort of Portuguese AD patients. We collected family history from patients with AD and cognitively healthy controls over 75 years of age. We compared the proportions of maternal and paternal history in male and female patients and controls (to search for evidence of X-linked and Y-linked inherited risk factors). We compared the risk of developing AD depending on parents' birthplace (same vs. different), as a proxy of remote consanguinity. We performed linear regressions to study the association of these variables with different endophenotypes. We included 3090 participants, 2183 cognitively healthy controls and 907 patients with AD. Men whose mother had dementia have increased odds of developing AD comparing to women whose mother had dementia. In female patients with a CSF biomarker-supported diagnosis of AD, paternal history of dementia is associated with increased CSF phosphorylated Tau levels. People whose parents are from the same town have higher risk of dementia. In multivariate analysis, this proxy is associated with a lower age of onset and higher CSF phosphorylated tau. Our study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity.
Sections du résumé
BACKGROUND
BACKGROUND
Alzheimer's disease (AD) heritability is estimated to be around 70-80%. Yet, much of it remains to be explained. Studying transmission patterns may help in understanding other factors contributing to the development of AD.
OBJECTIVE
OBJECTIVE
In this study, we aimed to search for evidence of autosomal recessive or X- and Y-linked inheritance of risk factors in a large cohort of Portuguese AD patients.
METHODS
METHODS
We collected family history from patients with AD and cognitively healthy controls over 75 years of age. We compared the proportions of maternal and paternal history in male and female patients and controls (to search for evidence of X-linked and Y-linked inherited risk factors). We compared the risk of developing AD depending on parents' birthplace (same vs. different), as a proxy of remote consanguinity. We performed linear regressions to study the association of these variables with different endophenotypes.
RESULTS
RESULTS
We included 3090 participants, 2183 cognitively healthy controls and 907 patients with AD. Men whose mother had dementia have increased odds of developing AD comparing to women whose mother had dementia. In female patients with a CSF biomarker-supported diagnosis of AD, paternal history of dementia is associated with increased CSF phosphorylated Tau levels. People whose parents are from the same town have higher risk of dementia. In multivariate analysis, this proxy is associated with a lower age of onset and higher CSF phosphorylated tau.
CONCLUSIONS
CONCLUSIONS
Our study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity.
Identifiants
pubmed: 39235525
doi: 10.1007/s00415-024-12673-x
pii: 10.1007/s00415-024-12673-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : R01AG067426
Pays : United States
Informations de copyright
© 2024. The Author(s).
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