PMID- 33888050

OWN - NLM
STAT- MEDLINE
DCOM- 20211029
LR - 20211204
IS - 1875-5828 (Electronic)
IS - 1567-2050 (Linking)
VI - 18
IP - 2
DP - 2021
TI - Multiomics Investigation of Hypertension and White Matter Hyperintensity as a
Source of Vascular Dementia or a Comorbidity to Alzheimer's Disease.
PG - 171-177
LID - 10.2174/1567205018666210422133547 [doi]
AB - 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.
CI - Copyright© Bentham Science Publishers; For any queries, please email at
epub@benthamscience.net.
FAU - Pathak, Gita A
AU - Pathak GA
AD - Department of Microbiology, Immunology & Genetics, University of North
Texas
Health Science Center Fort Worth, Texas 76107, United States.
FAU - Barber, Robert C
AU - Barber RC
AD - Department of Microbiology, Immunology & Genetics, University of North
Texas
Health Science Center Fort Worth, Texas 76107, United States.
FAU - Phillips, Nicole R
AU - Phillips NR
AD - Department of Microbiology, Immunology & Genetics, University of North
Texas
Health Science Center Fort Worth, Texas 76107, United States.
LA - eng
GR - U01 AG024904/AG/NIA NIH HHS/United States
GR - T32 AG020494/AG/NIA NIH HHS/United States
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, Non-P.H.S.
PL - United Arab Emirates
TA - Curr Alzheimer Res
JT - Current Alzheimer research
JID - 101208441
RN - 0 (Amyloid)
RN - 0 (Membrane Transport Proteins)
RN - 0 (Mitochondrial Precursor Protein Import Complex Proteins)
RN - 0 (Phosphoproteins)
RN - 0 (Sodium-Hydrogen Exchangers)
RN - 0 (TOMM40 protein, human)
RN - 0 (sodium-hydrogen exchanger regulatory factor)
RN - 0 (tau Proteins)
SB - IM
MH - Aged
MH - *Alzheimer Disease/cerebrospinal fluid/diagnosis/pathology
MH - Amyloid/cerebrospinal fluid
MH - Comorbidity
MH - *Dementia, Vascular/cerebrospinal fluid/diagnosis
MH - Female
MH - *Genome-Wide Association Study
MH - Humans
MH - Hypertension/*complications
MH - Male
MH - Membrane Transport Proteins/genetics
MH - Middle Aged
MH - Mitochondrial Precursor Protein Import Complex Proteins
MH - Phosphoproteins/genetics
MH - Sodium-Hydrogen Exchangers/genetics
MH - White Matter/*pathology
MH - tau Proteins/cerebrospinal fluid
OTO - NOTNLM
OT - *Alzheimer's disease
OT - *CSF biomarkers
OT - *comorbidity
OT - *hypertension
OT - *vascular dementia
OT - *white matter hyperintensity
EDAT- 2021/04/24 06:00
MHDA- 2021/10/30 06:00
CRDT- 2021/04/23 05:28
PHST- 2020/11/13 00:00 [received]
PHST- 2021/02/27 00:00 [revised]
PHST- 2021/04/06 00:00 [accepted]
PHST- 2021/04/24 06:00 [pubmed]
PHST- 2021/10/30 06:00 [medline]
PHST- 2021/04/23 05:28 [entrez]
AID - CAR-EPUB-115443 [pii]
AID - 10.2174/1567205018666210422133547 [doi]
PST - ppublish
SO - Curr Alzheimer Res. 2021;18(2):171-177. doi:
10.2174/1567205018666210422133547.