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The Role of Viral Exposure and Age in Alzheimer's Disease Progression

Award Number: R01AG082899
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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The Role of Viral Exposure and Age in Alzheimer's Disease Progression - Currently afflicting more than 6.2 million Americans, Alzheimer’s Disease (AD) is a chronic neurodegenerative condition that results from pathological brain aging and is the most common cause of cognitive dysfunction among older adults. The lack of comprehensive understanding regarding drivers of AD initiation and progression represents a critical barrier to progress for the field and has contributed to the current lack of viable treatment options. Pathogens are emerging as a potential contributor to the etiology of AD. Neurological manifestations and AD-associated phenotypes following acute infection with a variety of pathogens have been well documented. The long-term consequences of repeated infection are inadequately studied, though emerging epidemiological and preclinical evidence suggests that a higher lifetime infection burden impairs cognition, especially among organisms carrying AD genetic risk. That pathogens impact cellular metabolism may represent a key AD-related mechanism by which infection accelerates AD progression. What remains unknown is 1) whether a higher lifetime exposure frequency to pathogens, especially those that have limited neuronal tropism, can promote an AD phenotype, 2) how advanced age may potentiate this risk, and 3) the extent to which altered metabolism, due to infection, contributes to these effects. Determination of how repeated viral exposure influences AD neuropathological development and cognitive impairment as a function of age is a critical need for the field. Our preliminary data demonstrates that intermittent infection induces altered metabolic phenotypes in brain microvascular endothelial cells (BMVEC) and correlates with reduced cognitive function. We observe significant decreases in markers associated with mitochondrial function in infected mice. We will leverage an aging murine model with repeated exposure to viruses, to detect changes to metabolic pathways in the blood brain barrier and how this correlates to cognitive ability. Aim 1 will address if repeated viral exposure accelerates age-associated mitochondrial dysfunction of cells in the blood brain barrier, contributing to AD progression. Aim 2 will define how voltage dependent anion channel 1 mechanistically alters mitochondrial function in BMVEC with age. Aim 3, defines how viruses impacts blood brain barrier permeability as a function of age, accelerating AD progression. The outcome of these studies will contribute crucial understanding of how pathogen exposure influences AD progression and cognitive function. This project could potentially revealing novel therapeutic or preventative targets to prevent AD progression, offering hope to millions of patients and their caregivers.


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: 2025 ( Subtotal = $526,494 )
2025	2025	THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Aging Research	001	3	6/12/2025	NON-COMPETING CONTINUATION	$42,979
2025	2025	THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Aging Research	000	3	4/17/2025	NON-COMPETING CONTINUATION	$483,515
														Subtotal = $526,494

Issue Date FY: 2024 ( Subtotal = $514,902 )
2024	2024	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Aging Research	000	2	4/29/2024	NON-COMPETING CONTINUATION	$514,902
														Subtotal = $514,902

Issue Date FY: 2023 ( Subtotal = $519,364 )
2023	2023	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Aging Research	000	1	8/9/2023	NEW	$519,364
														Subtotal = $519,364

Grand Total All Awards = $1,560,760

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The Role of Viral Exposure and Age in Alzheimer's Disease Progression

Award Number: R01AG082899

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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