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Peripheral Biomarkers for Early Diagnosis of Mixed Pathologies in AD/ADRD

Award Number: R01AG082352
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Peripheral Biomarkers for Early Diagnosis of Mixed Pathologies in AD/ADRD - The overall goal of our proposed research is to develop robust premortem biomarkers for accurate and differential diagnosis of Alzheimer's disease (AD), non-AD tauopathies, Lewy body dementia (LBD), and their comorbidities. A pathological hallmark of AD and other tauopathies is the deposition of tau protein aggregates in the brain, whereas in LBD there is accumulation of α-synuclein (aSyn) aggregates. Strikingly, more than half of patients with clinically diagnosed AD or LBD have concomitant tau and aSyn co-pathologies at autopsy. Moreover, patients with mixed tau and aSyn pathologies often suffer from worse clinical outcomes. Currently, it is highly challenging to clinically differentiate AD, LBD, and mixed AD/LBD due to overlapping symptoms. Moreover, co-existence of aSyn pathology also occurs frequently in non-AD tauopathies. Recent advances in brain imaging and immunoassays of amyloid-β and phosphorylated tau (p-tau) have greatly facilitated diagnosis of typical AD. However, these assays fail to identify non-AD tauopathies and mixed AD/LBD. Therefore, alternative measures in easily accessible biospecimens are warranted, especially if they enable simultaneous detection of tau and aSyn aggregates in patients with mixed tauopathies and synucleinopathies. In preliminary studies, we have leveraged the newly emerged technology known as the real-time quaking-induced conversion assay (tau RT-QuIC) for specific detection of tau aggregates in the skin of patients with AD and non-AD tauopathies. In conjunction with recently established aSyn RT-QuIC, we are in a unique position to accurately diagnose patients with mixed tau and aSyn pathologies using easily accessible skin specimens. We hypothesize that skin tau and aSyn detected by RT-QuIC are novel biomarkers for early and differential diagnosis of mixed tauopathies/synucleinopathies in routine clinical practice. We propose to test this hypothesis by pursuing three Aims: 1) Establish dual skin RT-QuIC biomarker assays for mixed tauopathies/synucleinopathies using neuropathologically confirmed cases; 2) Assess skin tau and aSyn detected by RT-QuIC as reliable biomarkers for premortem diagnosis of mixed tauopathies and synucleinopathies; and 3) Evaluate skin tau/aSyn biomarker assays for improving the differential diagnosis of mixed tauopathies/synucleinopathies through longitudinal follow-up. This translational project is supported by rich clinical resources and a strong team of basic and clinical neuroscientists. The successful outcome of our proposal will establish a robust skin-based diagnostic test for mixed pathologies that is prevalent in AD and related dementias, thus facilitating better patient care and development of disease-modifying therapies.


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 = $719,976 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	000	3	4/11/2025	NON-COMPETING CONTINUATION	$661,202
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	001	3	6/18/2025	NON-COMPETING CONTINUATION	$58,774
														Subtotal = $719,976

Issue Date FY: 2024 ( Subtotal = $743,879 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	000	2	3/5/2024	NON-COMPETING CONTINUATION	$669,491
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	001	2	6/28/2024	NON-COMPETING CONTINUATION	$74,388
														Subtotal = $743,879

Issue Date FY: 2023 ( Subtotal = $756,004 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	000	1	5/24/2023	NEW	$756,004
														Subtotal = $756,004

Grand Total All Awards = $2,219,859

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Peripheral Biomarkers for Early Diagnosis of Mixed Pathologies in AD/ADRD

Award Number: R01AG082352

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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