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IMPORTANCE OF PERIODONTITIS IN THE INNATE IMMUNE REGULATION OF ALZHEIMER'S DISEASE

Award Number: R01AG078708
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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IMPORTANCE OF PERIODONTITIS IN THE INNATE IMMUNE REGULATION OF ALZHEIMER'S DISEASE - Project Summary/Abstract Albeit periodontal disease is a local chronic infectious inflammatory process affecting tissues supporting teeth, it can also have systemic consequences. Along these lines are reports that Alzheimer’s disease (AD) is epidemiologically associated with periodontal disease. Yet, the mechanisms underlying this association are not delineated. Our preliminary studies provide new evidence that a keystone periodontal pathogen Porphyromonas gingivalis (Pg) could enter the brain and exacerbate amyloid-b (Ab) accumulation, neuroinflammation, microglia activation, synapse loss, and cognitive and behavioral impairments in AD mice upon oral gavage infection. Microglia are the primary innate immune cells in the brain, and microglial activation is an invariable feature of AD pathology. The complement system also represents a major part of innate immunity, and microglia have been identified as the dominant source of C1q, the initiation factor of the classical complement pathway, in the brain. The objective of this application is to understand the importance of periodontitis in regulating microglial in AD, and the role of complement component C1q in microglial activation and AD progression. Based on the literature and our preliminary results, we hypothesize that periodontal infection and inflammation not only increase the severity of AD, but also increase the risk of AD, via potentiating Ab-primed microglial activation and sensitizing microglia for a heightened inflammatory response to subsequent pathogenic stimuli. In addition, periodontitis-associated persistent C1q activation is critical for microglial priming and activation, and the increased neurodegeneration in AD. We will test our hypothesis by pursuing two specific aims. Aim 1 will determine how periodontitis regulates microglial activation in AD using three different models of periodontitis. Aim 2 will determine the role of complement component C1q in microglial activation and AD development following Pg infection. Our proposed studies will provide novel and significant insights into the association between periodontal infection and AD. Understanding how a prevalent chronic infection like periodontitis modulates complement and microglial activation will advance our understanding of the mysterious etiology of AD. The knowledge obtained from these studies will provide a basis for targeting microbial etiology and periodontal therapy to ameliorate the clinical manifestations of AD and lower AD prevalence.


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 = $371,250 )
2026	2026	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	000	4	2/26/2026	NON-COMPETING CONTINUATION	$371,250
														Subtotal = $371,250

Issue Date FY: 2025 ( Subtotal = $363,825 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	001	3	6/9/2025	NON-COMPETING CONTINUATION	$29,700
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	000	3	3/7/2025	NON-COMPETING CONTINUATION	$334,125
														Subtotal = $363,825

Issue Date FY: 2024 ( Subtotal = $371,250 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	001	2	6/28/2024	NON-COMPETING CONTINUATION	$37,125
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	000	2	2/28/2024	NON-COMPETING CONTINUATION	$334,125
														Subtotal = $371,250

Issue Date FY: 2023 ( Subtotal = $371,250 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Aging Research	000	1	5/25/2023	NEW	$371,250
														Subtotal = $371,250

Grand Total All Awards = $1,477,575

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IMPORTANCE OF PERIODONTITIS IN THE INNATE IMMUNE REGULATION OF ALZHEIMER'S DISEASE

Award Number: R01AG078708

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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