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Impact of SARS-CoV-2 on the cerebrovasculature as a risk factor for VCID: Role of Wnt/beta-catenin

Award Number: R56NS138437
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract COVID-19 increases the risk of vascular contributions to cognitive impairment and dementia (VCID). VCID is one of the most prevalent forms of dementia, so the potential public health impact of the COVID-19 pandemic on future VCID is substantial. However, the mechanisms by which COVID-19 modifies VCID are unknown. Identifying mechanisms that regulate how prior COVID-19 influences the brain endothelial cell response to vascular stress is important. Here, we provide preliminary evidence that COVID-19 decreases resistance to VCID by weakening the blood-brain barrier (BBB). This is accompanied by cerebrovascular inflammation. This grant will test the novel mechanism that SARS-CoV-2 infection accelerates VCID by suppressing cerebrovascular Wnt/β-catenin signaling. In Aim 1, we determine how prior SARS-CoV-2 infection influences BBB permeability and cognition upon subsequent vascular insult, by genetic and epigenetic modification. In Aim 2 we use endothelial-targeted genetic interventions to assess the contribution of Wnt/β- cat targets to resistance to post-infectious VCID. In Aim 3, we ask whether established post-infectious VCID can be reversed by increasing cerebrovascular Wnt/β-catenin. These studies could lead to novel approaches to identify individuals at high risk for VCID and novel potential therapeutic strategies to mitigate the impact of prior infection on the development of dementia.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $561,155 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/15/2024	NEW	$0
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/8/2024	NEW	$559,650
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	8/21/2024	NEW	$1,505
														Subtotal = $561,155

Grand Total All Awards = $561,155

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Impact of SARS-CoV-2 on the cerebrovasculature as a risk factor for VCID: Role of Wnt/beta-catenin

Award Number: R56NS138437

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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