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Multiomics Investigation of Hypertension and White Matter Hyperintensity as a Source of Vascular Dementia or a Comorbidity to Alzheimer's Disease.
Current Alzheimer Research ( IF 1.8 ) Pub Date : 2021-04-22 , DOI: 10.2174/1567205018666210422133547
Gita A Pathak 1 , Robert C Barber 1 , Nicole R Phillips 1
Affiliation  

BACKGROUND Age-related comorbidity is common and significantly increases the burden for the healthcare of the elderly. Alzheimer's disease (AD) and hypertension are the two most prevalent age-related conditions and are highly comorbid. While hypertension is a risk factor for vascular dementia (VD), hypertension with AD (ADHyp+) is often characterized as probable vascular dementia. In the absence of imaging and other diagnostic tests, differentiating the two pathological states is difficult. OBJECTIVE Our goals are to (1) identify differences in CSF-based vascular dementia profiles, if any, between individuals who have AD only (ADHyp-), and individuals with ADHyp+ using CSF levels of amyloid β, tau and p-tau, and (2) compare genome-wide DNA profiles of ADHyp- and AD-Hyp+ with an unaffected control population. METHODS Genotype and clinical data were used to compare healthy controls to AD+/Hyp- vs AD+/Hyp+. We compared the CSF biomarkers followed by evaluating genome wide profiles in three groups, and mapped SNPs to genes based on position and lowest p-value. The significant genes were examined for co-expression and known disease networks. RESULTS We found no differences between Aβ, tau and p-tau levels between ADHyp- and AD- Hyp+. We found TOMM40 to be associated with ADHyp- as expected but not with ADHyp+. Inter- estingly, SLC9A3R2 polymorphism was associated with ADHyp+, and significant gene expression changes were observed for neighboring genes. CONCLUSION Through this exploratory study using a novel cohort stratification design, we highlight the genetic differences in clinically similar phenotypes, indicating the utility of genetic profiling in aiding differential diagnosis of ADHyp+ and VD.

中文翻译:

高血压和白色物质高血压作为血管性痴呆或阿尔茨海默氏病的合并症的多组学研究。

背景技术与年龄相关的合并症是常见的,并且显着增加了老年人保健的负担。阿尔茨海默氏病(AD)和高血压是两种最普遍的与年龄相关的疾病,并且是高度合并症。高血压是血管性痴呆(VD)的危险因素,而患有AD(ADHyp +)的高血压通常被表征为可能的血管性痴呆。在没有影像学检查和其他诊断检查的情况下,很难区分两种病理状态。目的我们的目标是(1)使用CSF淀粉样β,tau和p-tau的水平确定仅患有AD(ADHyp-)的人与患有ADHyp +的人之间基于CSF的血管性痴呆谱的差异(如果有)。 (2)将ADHyp-和AD-Hyp +的全基因组DNA谱图与未受影响的对照人群进行比较。方法采用基因型和临床数据比较健康对照者与AD + / Hyp-与AD + / Hyp +的对照。我们比较了CSF生物标志物,然后评估了三组的全基因组概况,并根据位置和最低p值将SNPs映射到了基因上。检查了重要基因的共表达和已知疾病网络。结果我们发现ADHyp-和AD- Hyp +之间的Aβ,tau和p-tau水平之间没有差异。我们发现,TOMM40与预期的ADHyp-相关,但与ADHyp +不相关。有趣的是,SLC9A3R2多态性与ADHyp +相关,并且观察到邻近基因的显着基因表达变化。结论通过一项采用新型队列分层设计的探索性研究,我们强调了临床相似表型的遗传差异,
更新日期:2021-04-22
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