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Identification of the genetic and transcriptomic networks of cognitive and neuropathological resilience to Alzheimer?s disease associated viruses

Award Number: U01AG061835
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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ABSTRACT Investigators have long suspected that pathogenic microbes might contribute to the onset or progression of Alzheimer’s disease (AD) although findings have been inconclusive, with reports of microbe-related antigens from entities as diverse as herpesviruses and borrelia species. Recent large-scale efforts such as the NIH Accelerating Medicines Partnership for Alzheimer’s disease (AMP-AD) are generating multiple forms of next- generation sequencing data on large, well-characterized AD cohorts and controls. These data present new opportunities to detect the presence of viral species directly from clinical samples and to put measures of viral species abundance into the context of the most molecular networks and clinical features. We plan to build upon our preliminary work that has identified consistently increased abundance of specific Herpesviridae species in post mortem brain tissue from individuals with AD, and demonstrated viral regulation of AD associated molecular, genetic and clinic-pathological networks. The Aims of this proposal are designed to illuminate the genetic, transcriptomic and proteomic host networks that confer cognitive and neuropathological resilience to these AD- associated viral species, with the goal of identifying novel therapeutic opportunities for the treatment of AD. This requires that we systematically characterize the impact of viral perturbations that are known or suspected to associate with a diagnosis of AD, amyloid plaque density, neurofibrillary tangle severity or clinical dementia ratings, and identify the host networks capable of modifying these relationships. By modelling the causal interactions that relate virus, host and disease, we can conceptualize these host molecules (and their appropriate perturbations) as potential mediators of resilience in the face of viral infection. We will validate genetic and small molecule perturbations of virally infected cerebral organoids systems, monitoring changes in resilience to viral infectivity, AD associated neuropathology markers, and host transcriptomics, including activity of targeted resilience networks. The expected outcome of this study is to identify and evaluate specific host molecular networks and small molecules that are capable of modulating host responses to infection with AD-relevant viruses.


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 = $0 )
2024	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	001	5	3/6/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	000	5	3/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	000	5	12/21/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $1,393,498 )
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	002	5	8/12/2022	SUPPLEMENT FOR EXPANSION	$288,779
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	001	5	8/11/2022	NON-COMPETING CONTINUATION	$1,104,719
2022	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	000	4	5/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,393,498

Issue Date FY: 2021 ( Subtotal = $1,163,147 )
2021	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	003	4	7/28/2021	NON-COMPETING CONTINUATION	$1,163,147
2021	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	004	4	8/26/2021	NON-COMPETING CONTINUATION	$0
2021	2020	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	002	3	5/6/2021	NON-COMPETING CONTINUATION	$0
2021	2019	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	001	2	2/12/2021	NON-COMPETING CONTINUATION	$0
2021	2018	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	000	1	2/11/2021	NEW	$0
														Subtotal = $1,163,147

Issue Date FY: 2020 ( Subtotal = $1,246,169 )
2020	2020	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	002	3	7/22/2020	NON-COMPETING CONTINUATION	$1,171,622
2020	2020	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	001	2	3/31/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2020	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	000	2	3/16/2020	SUPPLEMENT FOR EXPANSION	$74,547
														Subtotal = $1,246,169

Issue Date FY: 2019 ( Subtotal = $1,531,391 )
2019	2019	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	003	2	6/10/2019	NON-COMPETING CONTINUATION	$1,105,054
2019	2019	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	004	2	9/12/2019	SUPPLEMENT FOR EXPANSION	$426,337
2019	2018	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	002	1	1/21/2019	NEW	$1,125,901
2019	2018	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	001	1	1/16/2019	NEW	-$1,125,901
2019	2018	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Aging Research	000	1	1/14/2019	NEW	$0
														Subtotal = $1,531,391

Grand Total All Awards = $5,334,205

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Identification of the genetic and transcriptomic networks of cognitive and neuropathological resilience to Alzheimer?s disease associated viruses

Award Number: U01AG061835

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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