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Presenilin Knock-in Rat Model of Neurodegeneration

Award Number: K99AG065441
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/15/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2022

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Presenilin Knock-in Rat Model of Neurodegeneration - PROJECT SUMMARY/ABSTRACT Alzheimer's disease (AD) is the most common form of dementia in the elderly, and currently there exists no disease modifying therapy. Familial forms of AD (FAD) are caused by mutations in Amyloid Precursor Protein (APP), whose processing can result in the formation of amyloid beta (Aβ), or by mutations in Presenilin 1/2 (PSEN1/2), which comprise in part the γ-secretase complex that cleaves Aβ from fragments of APP. My long- term career goal is to study the mechanism of neurodegeneration in Alzheimer disease. The more proximate goal, as put forward in this proposal, is to characterize the neurodegeneration in a new rat knock-in model of Presenilin1 dysfunction. Psen1-knockout (Psen1-KO) mice and knock-in (KI) mice with homozygous FAD- associated L435F mutations (Psen1LF/LF) are embryonic and perinatally lethal, precluding a more rigorous examination of the effect of AD-causing Psen1 mutations on neurodegeneration. Given the better suitability of rats as a model organism, with regards to surgical interventions and behavior testing, we generated a rat KI model of the Psen1LF mutation. We find that, unexpectedly and in contrast to Psen1LF/LF, Psen1LF/LF rats survive into adulthood despite a loss of γ-secretase activity. The survival of these rats affords the opportunity to examine the effect of homozygous Psen1 AD mutations on neurodegeneration.


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 = -$32,603 )
2024	2022	RUTGERS, THE STATE UNIVERSITY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Aging Research	000	2	11/16/2023	NON-COMPETING CONTINUATION	-$32,603
														Subtotal = -$32,603

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Aging Research	000	2	2/7/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $113,884 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Aging Research	000	2	5/25/2022	NON-COMPETING CONTINUATION	$113,884
														Subtotal = $113,884

Issue Date FY: 2021 ( Subtotal = $113,884 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	185 S ORANGE AVE	NEWARK	NJ	07103	ESSEX	USA	Aging Research	000	1	5/7/2021	NEW	$113,884
														Subtotal = $113,884

Grand Total All Awards = $195,165

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Presenilin Knock-in Rat Model of Neurodegeneration

Award Number: K99AG065441

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/15/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2022

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