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Identifying the relationship between alcohol and Alzheimer's Disease

Award Number: R01AA029985
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Identifying the relationship between alcohol and Alzheimer's Disease - Project Summary / Abstract Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide, accounting for approximately half to two-thirds of all cases of dementia. It is associated with cognitive impairments and an increase in β-amyloid plaque (Aβ) deposits. Moreover, alcohol use disorder (AUD) has been associated with neurodegeneration and cognitive impairments, but the role of alcohol dependence on AD has been somewhat controversial. Recent evidence suggests a likely role for alcohol use as a risk factor in onset and severity of Alzheimer's disease, however overall reports have been mixed. Given the pervasive use of alcohol, it is critical to understand the potential impact of alcohol drinking on AD. We will examine the impact of a history of alcohol dependence on the onset and severity of behavioral and neuropathological symptoms associated with AD. We will further examine how alcohol dependence influences neural network function in AD. We will assess whether or not treatment with Memantine can reverse the behavioral and neuropathological symptoms. We hypothesize that a history of alcohol dependence will result in an earlier onset of cognitive impairment in AD mice as well as a greater presence of Aβ deposits and that these deficits will be rescued by chronic treatment with Memantine. We hypothesize that a history of alcohol dependence in AD mice will alter network connectivity (decrease modularity and change hub regions) and that these effects will be alleviated by Memantine treatment. Alterations of functional network connectivity that are caused by alcohol dependence will be assessed in a mouse model of AD. These changes will be compared with the brain-wide spread of Aβ deposits, which will indicate the way in which AD affects brain-wide function, potentially beyond brain areas with signs of neuropathology. Furthermore, the role of alcohol dependence in AD (e.g., changes in network connectivity and behavioral and neuropathological symptoms) will be examined using a relevant translational preclinical model of AUD. Cognitive function, anxiety-like behavior, and irritability-like behavior will be assessed in AD and wildtype alcohol drinking and alcohol naive mice. The number and location of Aβ deposits will be assessed AD mice. Differences in network connectivity in AD and wildtype mice will be examined using hierarchical clustering and graph theory. If alcohol dependence is found to impact the onset of neurological and behavioral symptoms of AD, then this will be a highly significant finding that will have a broad impact on preclinical and clinical research. These potential findings may also directly influence public guidelines for alcohol consumption, especially in those with a familial risk for AD.


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 = $343,345 )
2024	2024	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Alcohol Research Programs	000	3	7/3/2024	NON-COMPETING CONTINUATION	$343,345
														Subtotal = $343,345

Issue Date FY: 2023 ( Subtotal = $343,345 )
2023	2023	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Alcohol Research Programs	000	2	6/17/2023	NON-COMPETING CONTINUATION	$343,345
														Subtotal = $343,345

Issue Date FY: 2022 ( Subtotal = $343,345 )
2022	2022	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Alcohol Research Programs	000	1	9/19/2022	NEW	$343,345
														Subtotal = $343,345

Grand Total All Awards = $1,030,035

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Identifying the relationship between alcohol and Alzheimer's Disease

Award Number: R01AA029985

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/20/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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