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Low Level Laser Therapy in Alzheimer's Disease

Award Number: RF1AG058603
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Low Level Laser Therapy in Alzheimer's Disease - ABSTRACT Alzheimer’s disease (AD) is the most common form of dementia in the United States, affecting over 5 million Americans. Unfortunately, there are currently no effective therapeutic strategies to slow, halt, or reverse the advance of the disease. As a noninvasive procedure, Low-level Laser Therapy (LLLT) or photobiomodulation is widely practiced to stimulate healing, relieve pain, and reduce inflammation. Our previous studies on AD animal models and our preliminary data on a novel and clinically relevant transgenic rat model have shown that LLLT can strongly protect against AD pathological hallmarks and cognitive decline. This exciting observation has led to hope that further studies of LLLT neuroprotection against AD could potentially lead to new therapies in humans. The overall goal of the current proposal is to test the neuroprotective and cognitive improvement effects of LLLT on AD pathology, and to elucidate the underlying mechanisms. We hypothesize that leakage of blood hemoglobin (blood-Hb) into brain tissue through the compromised blood brain barrier (BBB) during AD progression aggregates Aβ plague formation, enhances oxidative stress and inflammation, and accelerates tauopathy. Alongside this, AD-induced mitochondrial fragmentation and energy depletion, as well as decreases in neuronal hemoglobin (Neu-Hb), weakens cellular resistance to Aβ toxicity. Collectively, AD induces extracellular Aβ deposits, aberrant intracellular mitochondrial fission and dysfunction, neurofibrillary tangles, and oxidative and inflammatory damage that ultimately culminate in neurodegeneration and cognitive decline. However, we hypothesize that LLLT can confer neuroprotective and cognitive benefits in AD pathology. We posit that these benefits result from LLLT’s ability to preserve healthy mitochondrial fission/fusion dynamics, thereby promoting mitochondrial function as well as enhancing endogenous heme biosynthesis. In addition, we propose that LLLT induced shifts in mitochondrial dynamics will potentiate nuclear translocation of HIF-1α to induce the target gene expression. On the one hand, the induced factors are able to protect and repair BBB damage, thereby reducing Aβ aggregation exacerbated by exogenous blood-Hb. On the other hand, HIF-1α-induced globin can be assembled with mitochondrial-produced heme to form Neu-Hb to exert beneficial effects. The proposed studies would advance the field by determining the potential efficacy of LLLT for protection of the AD brain. Specific Aim 1 would test the hypothesis that LLLT exerts neuroprotection and improves functional outcome in transgenic AD rats. Specific Aim 2 would test the hypothesis that preservation of mitochondrial dynamics and restoration of mitochondrial function underlies LLLT’s neuroprotective abilities. Specific Aim 3 would test the hypothesis that LLLT reduces Aβ aggregation and increases neuronal resistance/homeostasis via the activation of Mitochondria-HIF-1α-Hb pathway in AD pathological conditions.


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: 2024 ( Subtotal = -$273,738 )
2024	2018	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Aging Research	001	2	10/1/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$201,449
2024	2018	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Aging Research	000	2	10/1/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$72,289
														Subtotal = -$273,738

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2018	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Aging Research	000	2	11/1/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2018	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Aging Research	001	2	7/1/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$657,565
2022	2018	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Aging Research	002	1	9/13/2022	NEW	-$235,963
2022	2018	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Aging Research	003	2	9/13/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$235,963
2022	2018	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Aging Research	000	1	7/1/2022	NEW	-$657,565
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Aging Research	000	1	12/9/2019	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $1,916,563 )
2018	2018	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Aging Research	001	1	9/21/2018	NEW	$1,535,313
2018	2018	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Aging Research	000	1	7/6/2018	NEW	$381,250
														Subtotal = $1,916,563

Grand Total All Awards = $1,642,825

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Low Level Laser Therapy in Alzheimer's Disease

Award Number: RF1AG058603

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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