Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Liquid biopsies to evaluate the effect of a ketogenic diet on molecular circuitries associated with mild cognitive impairment

Award Number: R01AG084696
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2028

Group Awards By:

View Award Description

Liquid biopsies to evaluate the effect of a ketogenic diet on molecular circuitries associated with mild cognitive impairment - Project Summary The discovery of brain cells-derived small extracellular vesicles (sEV), broadly known as exosomes, has led to studies examining their role as `liquid biopsies' for Alzheimer's disease and related dementias (ADRD). sEV offer a unique, repeatable, and less invasive tool to discover molecular changes in multiple cell types of the brain during Alzheimer's disease (AD) pathogenesis. Here, we propose to test the usefulness of brain cells-derived sEV to discover the molecular pathways targeted by a dietary intervention against AD and to identify individuals responsive to such intervention. Earlier studies have shown the beneficial effects of ketogenic diet (KD) against ADRD, and we have developed a KD version known as a `Modified Mediterranean-Ketogenic Diet (MMKD)' with improved nutrition and compliance, and recently in a pilot study published its promising beneficial effects in individuals with amnestic mild cognitive impairment (aMCI). Based upon these exciting results, a phase II study (BEAT-AD: Brain Energy for Amyloid Transformation in AD, R01AG055122, PI: Craft) was initiated to test MMKD efficacy in adults with aMCI in comparison to a low-fat American Heart Association Diet (AHAD). In BEAT-AD, all participants (100 adults with aMCI) undergo comprehensive cognitive testing, brain MRIs, apoE genotyping, and metabolic profiling. Additional assessments include CSF analysis of AD biomarkers and PET imaging of the brain for amyloid and tau deposition, ketone uptake, and glucose metabolism. Together, these `gold-standard' measures will assess the efficacy of MMKD against AD but are unlikely to establish the effect of MMKD on key molecular determinants of aMCI brain. Additionally, there is no known blood-based biomarker to identify those individuals who would be most responsive to MMKD. To demonstrate the usefulness of sEV in understanding the molecular action of MMKD at the neuronal level, we obtained plasma samples from the completed pilot study and generated solid feasibility data, published recently in the journal Brain Communications. Based upon these exciting findings, we propose to further establish the effect of MMKD on glutamate-glutamate receptor-Aβ signaling, oxidative stress, and neuroinflammation in the BEAT-AD study. In this ancillary study, we will isolate various brain cells-derived sEV from the plasma of all 100 participants (both pre- and post-MMKD and –AHAD) and characterize in the following aims: Aim I: sEV characterization to assess the effect of MMKD intervention on glutamate signaling and synaptic plasticity-related biomarkers in individuals with aMCI; Aim II: sEV characterization to determine the effect of MMKD intervention on oxidative stress and neuroinflammation in individuals with aMCI; and Aim III: To characterize brain cells-derived sEV to predict response to MMKD intervention in individuals with aMCI. Outcomes will establish brain cells-derived sEV as liquid biopsies to non- invasively assess the effect of MMKD on molecular circuitries in the aMCI brain and their clinical application in screening individuals responsive to MMKD, leading to an evidence-based `personalized approach' to AD.


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 = $760,997 )
2026	2026	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	001	3	2/23/2026	NON-COMPETING CONTINUATION	$76,099
2026	2026	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	3	1/9/2026	NON-COMPETING CONTINUATION	$684,898
														Subtotal = $760,997

Issue Date FY: 2025 ( Subtotal = $752,765 )
2025	2025	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	001	2	8/4/2025	NON-COMPETING CONTINUATION	$61,450
2025	2025	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	2	11/22/2024	NON-COMPETING CONTINUATION	$691,315
														Subtotal = $752,765

Issue Date FY: 2024 ( Subtotal = $763,947 )
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	1	2/7/2024	NEW	$763,947
														Subtotal = $763,947

Grand Total All Awards = $2,277,709

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Liquid biopsies to evaluate the effect of a ketogenic diet on molecular circuitries associated with mild cognitive impairment

Award Number: R01AG084696

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer