Miguel Tábuas-Pereira, Catarina Bernardes, João Durães, Marisa Lima, Ana Rita Nogueira, Jorge Saraiva, Teresa Tábuas, Mariana Coelho, Kimberly Paquette, Kaitlyn Westra, Célia Kun-Rodrigues, Maria Rosário Almeida, Inês Baldeiras, José Brás, Rita Guerreiro, Isabel Santana
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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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Our study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447147/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Miguel Tábuas-Pereira, Catarina Bernardes, João Durães, Marisa Lima, Ana Rita Nogueira, Jorge Saraiva, Teresa Tábuas, Mariana Coelho, Kimberly Paquette, Kaitlyn Westra, Célia Kun-Rodrigues, Maria Rosário Almeida, Inês Baldeiras, José Brás, Rita Guerreiro, Isabel Santana\",\"doi\":\"10.1007/s00415-024-12673-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Alzheimer's disease (AD) heritability is estimated to be around 70-80%. 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引用次数: 0
摘要
背景:据估计,阿尔茨海默病(AD)的遗传率约为 70-80%。然而,其中大部分仍有待解释。研究遗传模式可能有助于了解导致阿尔茨海默病发病的其他因素:在这项研究中,我们的目的是在一大批葡萄牙 AD 患者中寻找风险因素的常染色体隐性遗传或 X 和 Y 连锁遗传的证据:我们收集了 75 岁以上 AD 患者和认知健康对照组的家族史。我们比较了男女患者和对照组的母系和父系病史比例(以寻找 X 连锁和 Y 连锁遗传风险因素的证据)。我们比较了父母出生地不同(相同与不同)导致的AD发病风险,以此作为远缘血缘关系的代表。我们进行了线性回归,以研究这些变量与不同内表型的关联:我们共纳入了 3090 名参与者,其中包括 2183 名认知健康的对照组和 907 名注意力缺失症患者。与母亲患有痴呆症的女性相比,母亲患有痴呆症的男性患痴呆症的几率更高。在经脑脊液生物标志物确诊为痴呆症的女性患者中,父辈的痴呆症病史与脑脊液磷酸化 Tau 水平的升高有关。父母来自同一城镇的人患痴呆症的风险更高。在多变量分析中,这种代理与较低的发病年龄和较高的 CSF 磷酸化 Tau 相关:我们的研究提供了证据,支持与X连锁遗传模式和远亲关系相关的AD发病风险增加。
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.
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: 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: 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: 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: Our study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity.
期刊介绍:
The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field.
In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials.
Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.