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

Synapse repair in Alzheimer's disease and related dementias

Award Number: R01AG096932
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

Group Awards By:

View Award Description

Synapse repair in Alzheimer's disease and related dementias - PROJECT SUMMARY Progressive cognitive decline in tauopathies, such as Alzheimer’s disease (AD), coincides with synapse deterioration in the brain. Synaptic mechanisms are critical modulators of cognition, yet little is known about how synapse function can impact the susceptibility of individuals to cognitive decline in tauopathy. Long-term potentiation (LTP) at synapses in the hippocampus, considered the physiological basis of memory formation, is impaired in tauopathy mouse models, and LTP impairment coincides with memory decline. KIdney/BRAin (KIBRA) is a postsynaptic protein that is required for hippocampus-dependent memory and for LTP expression at synapses. Reduced KIBRA protein levels in the human brain are associated with pathological tau accumulation and cognitive impairment in with tauopathy. Our previous work on a transgenic mouse model of tauopathy demonstrated that overexpression of the C-terminal domain of the KIBRA protein can repair synaptic dysfunction and reverse cognitive impairments caused by pathogenic tau. The KIBRA C-terminal domain interacts with protein kinase C (PKC) isoforms, which can phosphorylate synaptic proteins and modulate synapse strength. The potential applications of KIBRA for clinical translation in tauopathy have yet to be established. The central hypothesis of this proposal is that a KIBRA-based peptide can repair synapses and reverse memory loss in tauopathy by modulating the PKC phosphorylation of synapto-protective proteins. We designed a small cell permeable synthetic peptide derived from the KIBRA protein sequence (KBpep) that protects against synaptic plasticity impairment, synapse loss, and memory deficits in a transgenic mouse model of hyperacetylated pathological tau found in AD and other tauopathies (tauKQhigh mice). In Aim 1, we will determine the therapeutic impact of KBpep on memory and in vivo plasticity in transgenic mouse models of tauopathy. In Aim 2, we will determine the mechanistic impact of KBpep on synaptic function across human induced pluripotent stem cell (iPSC)-derived neuron and transgenic mouse models of tauopathy. In Aim 3, we will delineate how KBpep affects PKC isoforms and the coordinated phosphorylation of proteins linked to the restorative effects on synapses in tauopathy models. Our studies represent a foundational step toward understanding how KIBRA can be developed into a therapeutic to restore synapse function and cognitive processes despite the toxicity and pathology in the brain in AD and FTLD-tau. These findings will provide valuable insights towards harnessing the therapeutic potential of KIBRA function to protect against cognitive decline in tauopathies.


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 = $785,081 )
2026	2026	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	000	1	9/17/2026	NEW	$785,081
														Subtotal = $785,081

Grand Total All Awards = $785,081

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Synapse repair in Alzheimer's disease and related dementias

Award Number: R01AG096932

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer