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 ADHyp+
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 ADHyp+.
We found TOMM40 to be associated with ADHyp- as expected but not with ADHyp+. Interestingly,
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.