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Extracranial Brain Stimulation Reduces Metabolic Insufficiency Through Enhanced Cerebral Blood Flow in CVN-AD Alzheimer's Model

Award Number: R01AG074999
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Extracranial Brain Stimulation Reduces Metabolic Insufficiency Through Enhanced Cerebral Blood Flow in CVN-AD Alzheimer's Model - Alzheimer's disease is a progressive degenerative disorder of unclear etiology and disease-modifying treatments remain elusive. However, there are abnormalities in substrate delivery to the brain, altered capillary reactivity, neurovascular coupling, and hemodynamic responsiveness to metabolic stress, such as low glucose or spreading depression, in both the disease and animal models (CVN-AD). Our hypothesis is that transcranial alternating current electrical stimulation (tACS) can improve metabolic insufficiency in a dose dependent and dynamic manner in the CVN-AD animal model of Alzheimer's disease, modulating disease progression and degeneration. We will apply tACS through skull mounted electrodes first on a scheduled approach, comparing 10 and 40 Hz stimulation to enhance cerebral blood flow and improve substrate delivery to the brain, assisted by Dr.'s Peterchev and Schmidt. Further, we will test behavioral outcomes to assess the effects of chronic, scheduled tACS and sham tACS over 4 weeks, starting at the critical points of degeneration at 12 and 24 weeks of age in the CVN-AD model, assessing outcome with probe trial errors on a Barnes maze, cerebral blood flow, measures of neurodegeneration. As a second goal we will develop dynamic, metabolic need-based tACS, using closed loop approaches. Surrogate physiological markers will include electrical recordings, glucose recordings, and EEG signals of activity to augment blood flow in a dynamic manner to improve immediate metabolic substrate supply and reduce degeneration. These experiments will establish the feasibility and parameters to translate into initial human studies using either semi-permanent skull mounted or temporary skin electrodes. Since current density and intracranial penetration of tACS is limited in humans various translational strategies will be devised to include dynamic biomarkers and appropriate stimulation levels through subcutaneous electrodes.


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 = $326,025 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	000	4	3/4/2025	NON-COMPETING CONTINUATION	$326,025
														Subtotal = $326,025

Issue Date FY: 2024 ( Subtotal = $362,250 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	000	3	1/23/2024	NON-COMPETING CONTINUATION	$326,025
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	001	3	6/25/2024	NON-COMPETING CONTINUATION	$36,225
														Subtotal = $362,250

Issue Date FY: 2023 ( Subtotal = $362,250 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	000	2	1/31/2023	NON-COMPETING CONTINUATION	$362,250
														Subtotal = $362,250

Issue Date FY: 2022 ( Subtotal = $373,113 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Aging Research	000	1	1/24/2022	NEW	$373,113
														Subtotal = $373,113

Grand Total All Awards = $1,423,638

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Extracranial Brain Stimulation Reduces Metabolic Insufficiency Through Enhanced Cerebral Blood Flow in CVN-AD Alzheimer's Model

Award Number: R01AG074999

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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