Tábuas-Pereira Miguel, Bernardes Catarina, Durães João, Lima Marisa, Nogueira Ana Rita, Saraiva Jorge, Tábuas Teresa, Coelho Mariana, Paquette Kimberly, Westra Kaitlyn, Kun-Rodrigues Célia, Almeida Maria Rosário, Baldeiras Inês, Brás José, Guerreiro Rita, Santana Isabel
Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
J Neurol. 2024 Oct;271(10):6983-6990. doi: 10.1007/s00415-024-12673-x. Epub 2024 Sep 5.
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.
阿尔茨海默病（AD）的遗传度估计约为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理解导致AD发生的其他因素。
在本研究中，我们旨在在一大群葡萄牙AD患者中寻找危险因素的常染色体隐性或X连锁及Y连锁遗传证据。
我们收集了AD患者以及75岁以上认知健康对照者的家族史。我们比较了男性和女性患者及对照者中母系和父系家族史的比例（以寻找X连锁和Y连锁遗传危险因素的证据）。我们比较了根据父母出生地（相同与不同）患AD的风险，将其作为远亲关系的替代指标。我们进行线性回归以研究这些变量与不同内表型的关联。
我们纳入了3090名参与者，2183名认知健康对照者和907名AD患者。母亲患有痴呆症的男性患AD的几率高于母亲患有痴呆症的女性。在脑脊液生物标志物支持诊断为AD的女性患者中，父亲的痴呆家族史与脑脊液磷酸化Tau水平升高有关。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，这一替代指标与发病年龄较低和脑脊液磷酸化tau水平较高有关。
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。
