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Immune cell activation and associated blood brain barrier changes across different stages of Alzheimer's disease

Award Number: R01AG078763
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Immune cell activation and associated blood brain barrier changes across different stages of Alzheimer's disease - PROJECT SUMMARY/ABSTRACT Age-related diseases, such as Alzheimer's disease (AD), are defining public health concerns of the 21st century and are the leading cause of disability worldwide. A growing body of evidence notes that central nervous system immune changes superimposed on ongoing chronic neurodegeneration may have a major impact on disease progression in AD and other neurodegenerative conditions. The role of the peripheral immune system in AD, including cellular elements of both the innate and adaptive immunity are still enigmatic. In this proposal, we investigate immune cell identity and abundance in the periphery and cerebrospinal fluid (CSF) at single cell resolution among preclinical-AD, MCI-AD, and AD-Dementia stages and among normal aging controls. Furthermore, a novel aspect of this study will be to corroborate the severity of blood brain barrier (BBB) changes associated with specific immune cell profiles noted in CSF and the periphery across AD stages and its impact on longitudinal cognitive decline. Our overall goal is to characterize immune cell identity and abundance in the periphery and the CNS at single cell resolution across different AD clinical stages and in tandem, to clarify the peripheral anatomical context of immune cell activation and the degree of BBB changes, with the goal of understanding the temporal course of immune response in relation to initiation of clinical decline and subsequent phenotypic heterogeneity of AD trajectories. Towards this, we will investigate immune cell phenotypes in the CSF and peripheral blood by a powerful single-cell proteomic analysis technique, mass cytometry, and BBB changes will be delineated by dynamic contrast-enhanced MRI techniques in the same subjects. Data integrating peripheral and CSF adaptive and innate immune cell activation along with BBB changes across different stages of AD will help develop a clear rationale for the use of these markers in the AmyloidTau(Neurodegeneration) framework. Additionally, these insights will help future therapeutic targeting of specific immune and BBB changes at the most effective clinical stage of disease. The results from the study will also enable the identification of novel mechanisms that regulate immune cell homeostasis in the periphery and the CNS, and the state of BBB, providing potential means to manipulate these immune cells for therapeutic purposes in the future.


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 = $738,231 )
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	3	7/9/2025	NON-COMPETING CONTINUATION	$738,231
														Subtotal = $738,231

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	2	6/14/2024	NON-COMPETING CONTINUATION	$0
2024	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	001	2	7/1/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $753,300 )
2023	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	001	2	5/22/2023	NON-COMPETING CONTINUATION	$753,300
2023	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	1	10/19/2022	NEW	$0
														Subtotal = $753,300

Issue Date FY: 2022 ( Subtotal = $779,250 )
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Aging Research	000	1	8/22/2022	NEW	$779,250
														Subtotal = $779,250

Grand Total All Awards = $2,270,781

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Immune cell activation and associated blood brain barrier changes across different stages of Alzheimer's disease

Award Number: R01AG078763

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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