@article{f24b99310bf24325b1a0338ca3088c51,
title = "Multiomics investigation of hypertension and white matter hyperintensi-ty as a source of vascular dementia or a comorbidity to alzheimer{\textquoteright}s disease",
abstract = "Background: Age-related comorbidity is common and significantly increases the bur-den for the healthcare of the elderly. Alzheimer{\textquoteright}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 pathologi-cal 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. Method: 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.",
keywords = "Alzheimer's disease, CSF biomarkers, Comorbidity, Hypertension, Vascular dementia, White matter hyperintensity",
author = "Pathak, {Gita A.} and Barber, {Robert C.} and Phillips, {Nicole R.}",
note = "Funding Information: We also appreciate the data received via authorized access from ADNI. Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). Funding Information: We like to acknowledge the NIH - Neurobiology of Aging T32 grant AG020494 for supporting this research. This project was supported in part by the Texas Alzheimer{\textquoteright}s Research and Care Consortium by the Darrell K Royal Texas Alzheimer{\textquoteright}s Initiative, directed by the Texas Council on Alzheimer{\textquoteright}s Disease and Related Disorders. Funding Information: We like to acknowledge the NIH-Neurobiology of Aging T32 grant AG020494 for supporting this research. This project was supported in part by the Texas Alzheimer?s Research and Care Consortium by the Darrell K Royal Texas Alzheimer?s Initiative, directed by the Texas Council on Alzheimer?s Disease and Related Disorders. We also appreciate the data received via authorized ac-cess from ADNI. Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineer-ing, and through generous contributions from the following: AbbVie, Alzheimer?s Association; Alzheimer?s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Bio-gen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogs-tate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Health-care; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lund-beck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servi-er; Takeda Pharmaceutical Company; and Transition Thera-peutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Pri-vate sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer?s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2021 Bentham Science Publishers.",
year = "2021",
doi = "10.2174/1567205018666210422133547",
language = "English",
volume = "18",
pages = "171--177",
journal = "Current Alzheimer Research",
issn = "1567-2050",
publisher = "Bentham Science Publishers B.V.",
number = "2",
}