Potential Modifying Effect of the APOEε4 Allele on Age of Onset and Clinical Manifestations in Patients with Early-Onset Alzheimer's Disease with and without a Pathogenic Variant in PSEN1 in a Sample of the Mexican Population.
Potential Modifying Effect of the APOEε4 Allele on Age of Onset and Clinical Manifestations in Patients with Early-Onset Alzheimer's Disease with and without a Pathogenic Variant in PSEN1 in a Sample of the Mexican Population.
复制标题
DOI：
10.3390/ijms242115687
复制
发表时间：
2023-10-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
在阿尔茨海默病（AD）中，发病年龄（AoO）表现出相当大的变异性，从40岁到90岁不等。具体来说，在65岁之前被诊断为AD并表现出症状的个体通常被归类为早发性（EOAD）病例。值得注意的是，载脂蛋白E (APOE) ε4等位基因代表了与AD相关的最广泛研究的遗传危险因素。我们对101例诊断为EOAD的患者进行了APOEε4等位基因的临床鉴定和分型，其中69例为常染色体显性全渗透PSEN1变异体c.1292C> a （rs63750083, A431E）的携带者（PSEN1+组），32例遗传原因未知（PSEN1−组）。我们发现AoO和APOEε4等位基因之间存在相关性；携带至少一个APOEε4等位基因的患者在PSEN1+组和PSEN1 -组中分别表现出3.9年（p = 0.001）和8.6年（p = 0.012）的AoO延迟。与PSEN1 -组相比，PSEN1+组出现步态障碍的频率更高，PSEN1+/APOE4+组出现失用的频率高于其他亚组。本研究显示APOEε4在EOAD患者中似乎具有相反的作用，因为它延迟AoO并改变临床表现。
In Alzheimer’s disease (AD), the age of onset (AoO) exhibits considerable variability, spanning from 40 to 90 years. Specifically, individuals diagnosed with AD and exhibiting symptoms prior to the age of 65 are typically classified as early onset (EOAD) cases. Notably, the apolipoprotein E (APOE) ε4 allele represents the most extensively studied genetic risk factor associated with AD. We clinically characterized and genotyped the APOEε4 allele from 101 individuals with a diagnosis of EOAD, and 69 of them were affected carriers of the autosomal dominant fully penetrant PSEN1 variant c.1292C>A (rs63750083, A431E) (PSEN1+ group), while there were 32 patients in which the genetic cause was unknown (PSEN1− group). We found a correlation between the AoO and the APOEε4 allele; patients carrying at least one APOEε4 allele showed delays, in AoO in patients in the PSEN1+ and PSEN1− groups, of 3.9 (p = 0.001) and 8.6 years (p = 0.012), respectively. The PSEN1+ group presented higher frequencies of gait disorders compared to PSEN1− group, and apraxia was more frequent with PSEN1+/APOE4+ than in the rest of the subgroup. This study shows what appears to be an inverse effect of APOEε4 in EOAD patients, as it delays AoO and modifies clinical manifestations.
登录
查看更多内容
DOI：
10.1016/j.trci.2018.09.006
发表时间：
2018
期刊：
Alzheimer's & dementia (New York, N. Y.)
影响因子：
--
作者：
Liu L;Caselli RJ
通讯作者：
Caselli RJ
影响因子：
5.1
作者：
通讯作者：
--
影响因子：
5.6
作者：
Lanfranco MF;Ng CA;Rebeck GW
通讯作者：
Rebeck GW
影响因子：
2.3
作者：
Calderon-Garciduenas, Ana Laura;Duyckaerts, Charles
通讯作者：
Duyckaerts, Charles
DOI：
10.1002/ajmg.c.31865
发表时间：
2020-12-04
影响因子：
3.1
作者：
Dumois-Petersen, Sofia;Gallegos-Arreola, Martha P.;Figuera, Luis E.
通讯作者：
Figuera, Luis E.