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Tau-induced connectome imaging markers of Alzheimer's disease

Award Number: R01AG064584
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Tau-induced connectome imaging markers of Alzheimer's disease - Abstract Hyperphosphorylated tau tangle is a defining hallmark of the Alzheimer’s disease (AD). Neuropathological and recent tau PET imaging studies suggest that tau deposition has a much stronger correlation with clinical symptoms than do amyloid plaques. The Braak staging suggests the neuron-to-neuron propagation of tau pathology through axonal pathways, which has been supported with increasing evidence from animal and post- mortem human studies. Limited research, however, has been conducted for the in vivo examination of connectivity changes of fiber pathways involved in tau pathology propagation. There is thus a clear knowledge gap regarding WHEN (specific tau pathology stage) and WHERE (specific fiber pathways) tau-induced connectivity changes occur during the disease course of AD. Building upon our extensive track record in connectome modeling and brain surface mapping, in this project we will develop novel computational tools for the systematic examination of different types of fiber pathways involved in the propagation of tau pathology: the short association fibers in the superficial white matter (SWM), the long association fibers within each hemisphere, and the commissural fibers connecting the two hemispheres. Our project will leverage existing tau PET and connectome imaging datasets that include: ADNI3 for late onset AD (LOAD) and the Estudio de la Enfermaded de Alzheimer en Jalisciences (EEAJ) study for autosomal dominant AD (ADAD). This provides us the unique opportunity to study ADAD and LOAD as being on an AD continuum and obtain a more complete characterization of the fiber pathways affected by the tau pathology from the early prodromal stage to the ultimate onset of AD. In addition, we will use an independent dataset (n=2000) from the Health & Aging Brain among Latino Elders (HABLE) study to validate the generalizability of our computational tools and connectome imaging makers to the Mexican American population. There are three specific aims in this project: 1. To develop novel computational tools for measuring superficial and deep white matter connectivity associated with tau propagation. 2. To map tau-induced connectivity changes of fiber pathways in AD. 3. To develop connectome-based prediction of tau- related cognitive changes in AD. Our project will for the first time provide the comprehensive and in vivo characterization of the fiber pathways affected by tau pathology in AD. This will help elucidate the role of different fiber pathways in the propagation of tau pathology at different disease stages, in particular the U-fibers in the SWM and the commissural fibers responsible for inter-hemispheric communications. The results from our study will provide more targeted connectome imaging makers for the early prediction of AD, especially in studies without tau PET imaging. All computational tools developed in this project will be freely distributed to the research community to enable other AD imaging researchers for more robust and thorough investigation of tau pathology networks.


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 = $478,696 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Aging Research	000	2	3/11/2025	EXTENSION WITH OR WITHOUT FUNDS	$478,696
														Subtotal = $478,696

Grand Total All Awards = $478,696

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Tau-induced connectome imaging markers of Alzheimer's disease

Award Number: R01AG064584

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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