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Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes - Diversity Supplement (Antwan Howard)

Award Number: R01AG062566
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/15/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes - Diversity Supplement (Antwan Howard) - Abstract of the Funded Project (R01 AG062566). Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease found at autopsy that underlies a variety of clinical dementia syndromes, and is the second most common cause of dementia under age 65 [1]. Patients with FTLD-related dementias are underserved in part because the complex relationship between dementias and underlying pathology is not well understood. Much of the complexity lies in the fact that the same pathology can cause different dementia syndromes and, conversely, that a single dementia syndrome can be caused by multiple pathologies. The goal of this proposal is to disentangle the complex relationship between dementia syndromes, anatomic atrophy, cell death, and a specific form of FTLD, known as FTLD-tau. In doing so, this work will help identify the putative substrates of neurodegeneration in FTLD-tau. This study focuses on a robust cohort of postmortem human specimens that show the most common forms of FTLD-tau: Pick’s disease and the frontotemporal lobar tauopathies of the corticobasal and progressive supranuclear palsy types (CBD-PSP). These tauopathies can underlie primary progressive aphasia (PPA), a clinical dementia syndrome characterized by progressive language impairment, and behavioral variant frontotemporal dementia (bvFTD), a clinical dementia syndrome characterized by progressive changes in comportment. Aim 1 will determine the specific targets and cellular features of a single tauopathy (Pick’s disease) in cases diagnosed antemortem with different dementia syndromes: the semantic and agrammatic variants of PPA (PPA-S and PPA-G, respectively) and bvFTD. These dementia syndromes are each associated with distinct patterns of atrophy and clinical profiles, providing an ideal model to explore the selective vulnerabilities of anatomic regions responsible for cognition or behavior. Aim 2 will study the converse relationship by investigating multiple pathologies (Pick’s disease and CBD-PSP) in cases diagnosed antemortem with a single dementia syndrome (PPA-G or bvFTD). Histological and unbiased stereological methods will be used to determine relationships between FTLD-tau pathology, not only to detailed clinical profiles and quantitative MRI atrophy patterns, but also to neuronal, glial, and synaptic abnormalities. A central hypothesis of this work is that regional distributions of FTLD-tau—and related cellular features—will show concordance with anatomic patterns of atrophy and distinct clinical profiles. This is one of the first works of its kind that aims to establish clinical, anatomic, and pathologic concordance of high specificity between clinical dementia syndromes and the tauopathies that cause them. PPA and bvFTD, specifically, offer exciting opportunities for exploring the organization and pathologic targets of anatomic networks in neurodegenerative diseases. Outcomes of this multidisciplinary study will clarify the pathologic underpinnings of clinical heterogeneity in dementias, sharpen our understanding of the principles of selective vulnerability, and are highly relevant for the development of tauopathy-specific diagnostic tools and treatments.


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: 2026 ( Subtotal = $0 )
2026	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	001	5	1/1/2026	SUPPLEMENT FOR EXPANSION	$0
2026	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	000	5	12/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $436,154 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	000	5	12/14/2023	NON-COMPETING CONTINUATION	$360,000
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	002	5	6/7/2024	NON-COMPETING CONTINUATION	$40,000
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	001	5	1/22/2024	SUPPLEMENT FOR EXPANSION	$36,154
														Subtotal = $436,154

Issue Date FY: 2023 ( Subtotal = $410,742 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	001	4	2/1/2023	SUPPLEMENT FOR EXPANSION	$10,742
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	000	4	1/31/2023	NON-COMPETING CONTINUATION	$400,000
														Subtotal = $410,742

Issue Date FY: 2022 ( Subtotal = $432,227 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	002	3	5/2/2022	NON-COMPETING CONTINUATION	$40,000
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	001	3	12/10/2021	SUPPLEMENT FOR EXPANSION	$32,227
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	000	3	12/9/2021	NON-COMPETING CONTINUATION	$360,000
														Subtotal = $432,227

Issue Date FY: 2021 ( Subtotal = $418,017 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	001	2	4/26/2021	SUPPLEMENT FOR EXPANSION	$21,350
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	000	2	1/28/2021	NON-COMPETING CONTINUATION	$396,667
														Subtotal = $418,017

Issue Date FY: 2020 ( Subtotal = $395,000 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	000	1	1/14/2020	NEW	$395,000
														Subtotal = $395,000

Grand Total All Awards = $2,092,140

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Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes - Diversity Supplement (Antwan Howard)

Award Number: R01AG062566

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/15/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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