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Development of sensitive PET tracers of pan-Amyloid-beta species for Alzheimer's disease

Award Number: R01AG085562
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Development of sensitive PET tracers of pan-Amyloid-beta species for Alzheimer's disease - The recent FDA approval of Leqembi (Lecanemab) for Alzheimer’s disease (AD) has spurred great optimism, and this approval also likely opens a door for preventive treatment for AD. However, currently available PET tracers have limited capacity for this preventive purpose. More sensitive new PET tracers are highly desirable. Amyloid beta (Aβ), is an appealing AD biomarker, as significant initial deposits of Aβ precede Tau pathology. Accordingly, the 2018 A/T/N Research Framework published by NIA-AA (National Institute of Ageing and Alzheimer’s Association) suggests that Aβs are the earliest biomarkers for AD before the appearance of irreversible neurologic syndromes. Aβ species can be categorized into soluble and insoluble species. Studies show that soluble Aβs, such as oligomers, are more neurotoxic than insoluble deposits (fibrils and plaques) and serve as biomarkers for pre- symptomatic stages of AD. In fact, abnormal Aβ levels in brains appear 30 years before symptoms are observed in humans. Unfortunately, the first-generation (1stG) Aβ PET probes are insensitive and only marginally detect abnormal Aβ deposits ~ 5 years before clinical AD syndrome diagnosis. This leaves a 25-year gap for which AD will progress undetectable. The intrinsic limitation of the 1stG PET tracers is their insensitivity to soluble Aβs, the best biomarker for pre-symptomatic AD. Preliminary results from the PI’s group over the past ten years suggest that this intrinsic limitation can be overcome with CRANAD-Xs, a series of probes capable of detecting not only insoluble Aβs but also soluble Aβs in vitro and in vivo. In this application, we propose to adapt our fluorescent CRANAD-X probes into sensitive Aβ PET tracers to fill the 25-year gap. Expected long-term impact. The proposed Aβ PET tracers will allow more sensitive detection vs. 1stG PET tracers and consequentially allow identification of AD patients at an earlier pre-symptomatic stage that is likely more responsive to treatment.


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 = $744,059 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	000	3	12/15/2025	NON-COMPETING CONTINUATION	$744,059
														Subtotal = $744,059

Issue Date FY: 2025 ( Subtotal = $810,197 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	001	2	8/12/2025	NON-COMPETING CONTINUATION	$66,138
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	000	2	11/22/2024	NON-COMPETING CONTINUATION	$744,059
														Subtotal = $810,197

Issue Date FY: 2024 ( Subtotal = $826,732 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	000	1	12/4/2023	NEW	$826,732
														Subtotal = $826,732

Grand Total All Awards = $2,380,988

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Development of sensitive PET tracers of pan-Amyloid-beta species for Alzheimer's disease

Award Number: R01AG085562

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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