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Temporal Associations of Neuroinflammation with Alzheimer’s Disease Biomarkers and Cognition

Award Number: R01AG102933
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Temporal Associations of Neuroinflammation with Alzheimer’s Disease Biomarkers and Cognition - PROJECT SUMMARY / ABSTRACT Alzheimer's disease (AD) is characterized by the deposition of β-amyloid in the brain, followed by tau accumulation, neurodegeneration, and cognitive decline. β-amyloid has been a primary target for AD therapies and studies to date have shown a modest slowing of cognitive decline. Targeting additional processes associated with AD pathology, such as neuroinflammation, may allow for more effective treatments. Critical knowledge gaps regarding the role of neuroinflammation in AD that must be answered for effective therapeutic targeting include the degree to which neuroinflammation is associated with changes in amyloid and tau deposition across disease stages and when in the AD continuum neuroinflammation plays a key role in promoting disease progression. The overall goal of this work is to determine the temporal evolution of neuroinflammation relative to AD biomarkers and cognitive decline. The first aim of the grant is to evaluate the association of baseline and longitudinal change in neuroinflammation with change in PET and plasma AD biomarkers across the disease spectrum. The second aim will evaluate the association of baseline and change in neuroinflammation with change in cognitive metrics. These first two aims will determine whether neuroinflammation PET may be a useful predictor of AD biomarker and cognitive progression and how those associations vary with disease stage (e.g., in amyloid positive, A+, vs amyloid negative, A-, and cognitively unimpaired, CU, vs impaired individuals). The third aim will evaluate cross-sectional and longitudinal associations of blood-based biomarkers of neuroinflammation with neuroinflammation PET to inform the ability of more accessible blood-based biomarkers to reflect degree of neuroinflammation as measured on PET and track longitudinal change. We will prospectively recruit 240 participants spanning the AD spectrum (CU A-, CU A+, mild cognitive impairment A+, and dementia due to AD) from Mayo Clinic Study of Aging (MCSA) and Mayo Alzheimer's Disease Research Center (ADRC) to undergo neuroinflammation PET (11C-ER176 TSPO PET) and continue to follow a preliminary TSPO PET cohort (N=96). Participants will undergo routine assessments per the standardized MCSA/ADRC protocols including cognitive assessments and blood draws at approximately 15-month intervals and imaging (MRI, amyloid PET, tau PET) at approximately 30-month intervals. This grant will add TSPO PET to the imaging visit and blood analysis for neuroinflammation markers. This study is significant as it will inform the temporal evolution of neuroinflammation in AD, how and when neuroinflammation affects AD progression, and thereby define appropriate therapeutic windows for targeting neuroinflammation along the disease spectrum and inform the utility of TSPO PET as a predictor of disease progression and clinical trial enrichment.


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 = $677,880 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	1	9/29/2026	NEW	$677,880
														Subtotal = $677,880

Grand Total All Awards = $677,880

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Temporal Associations of Neuroinflammation with Alzheimer’s Disease Biomarkers and Cognition

Award Number: R01AG102933

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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