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Innovating high-resolution novel imaging approaches to elucidate mechanisms of prion-like spreadingof neurodegenerative disease

Award Number: R01AG064051
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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An exciting new area in neurodegenerative disease research is the emerging phenomenon of prion-like spreading of neurodegenerative disease proteins. Prions are well established as the protein-based infectious agent underlying the spongioform encephalopathies. In these rare, albeit devastating, diseases the prion protein converts from the normal soluble form to the aggregated self-templating infectious form. This process initiates an inexorable spread of pathology and contingent neurodegeneration throughout the brain. But could this disease mechanism extend to the more common neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease and related dementia? If so, it represents a game changer in terms of understanding disease mechanisms and opens many new avenues for therapeutic development. However, any therapeutic or mechanistic investigation into prion-like spreading will require the development of powerful new imaging approaches to track the path of prion-like spread and understand how these protein aggregates alter brain function as they spread. We will need to understand why they take some routes but not others and how this impacts brain function. To address this challenge, we have formed an interdisciplinary team, consisting of an engineer and a geneticist. First, we will use state of the art brain clearing technology to obtain high-resolution images of prion-like protein propagation of the Parkinson’s disease protein a-synuclein. We will monitor these aggregates as they spread from one neuron to the next, tracking their paths. These high-resolution brain wide 3D maps of alpha-synuclein spreading will empower us to identify gene expression patterns associated with spreading paths and to nominate genes for functional studies. Then, we will utilize advanced high-resolution optogenetic functional magnetic resonance imaging (ofMRI) to reveal the longitudinal effects of prion-like spreading on brain network activity and likewise the impact of neural activity on prion-like spreading. Our experiments will provide fundamental mechanistic insight into prion-like spread of neurodegenerative disease. The tools we apply and the lessons we learn will likely be broadly applicable to neurodegenerative diseases including Alzheimer’s disease and related dementias.


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: 2023 ( Subtotal = $601,347 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	4	6/16/2023	NON-COMPETING CONTINUATION	$601,347
														Subtotal = $601,347

Issue Date FY: 2022 ( Subtotal = $601,915 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	3	3/18/2022	NON-COMPETING CONTINUATION	$541,722
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	001	3	6/13/2022	NON-COMPETING CONTINUATION	$60,193
														Subtotal = $601,915

Issue Date FY: 2021 ( Subtotal = $654,453 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	001	2	3/17/2021	NON-COMPETING CONTINUATION	$604,813
2021	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	1	2/2/2021	NEW	$49,640
														Subtotal = $654,453

Issue Date FY: 2020 ( Subtotal = $607,625 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	1	4/23/2020	NEW	$607,625
														Subtotal = $607,625

Grand Total All Awards = $2,465,340

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Innovating high-resolution novel imaging approaches to elucidate mechanisms of prion-like spreadingof neurodegenerative disease

Award Number: R01AG064051

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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