Monday, February 16, 2026 2/16/2026

Molecular Mechanisms of Synergistic TDP-43 and Tau Proteotoxicity in Alzheimer's Disease

Award Number: K08AG065426
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/15/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2024

Group Awards By:

View Award Description

Molecular Mechanisms of Synergistic TDP-43 and Tau Proteotoxicity in Alzheimer's Disease - Abstract There are currently no disease modifying therapies for AD but many disease-relevant pathways remain under- explored. This proposal seeks to understand the molecular mechanisms relating tau and TDP-43 pathology in the context of late-onset Alzheimer’s disease (AD) by combining human neuropathology and gene expression data with biological validation in a C. elegans model of proteotoxicity. Under the mentorship of Drs. Brain Kraemer and Dirk Keene, this training and research plan will build on Dr. Latimer’s expertise in neuropathology and prepare her for a career studying the proteotoxic pathways relevant to AD using C. elegans as a model system. C. elegans represent an ideal system for investigating mechanisms of human disease given their ease of transgenic modification, short life cycle, and recapitulation of the progressive neurodegeneration that is characteristic of human proteinopathies. The five-year training plan includes research mentored by an established team of experts and instruction in C. elegans research techniques, classification of TDP-43 proteinopathy, implementation of quantitative algorithms for immunohistochemistry in human tissue, and analysis and interpretation of RNA-Seq data. This training will provide Dr. Latimer with the interdisciplinary skills and knowledge necessary to achieve her long-term career goal to succeed as an independent physician scientist with the expertise to advance the field of AD pathophysiology using C. elegans models of proteotoxicity to link human pathology with the underlying mechanisms. Data from human cohorts suggest a role for TDP-43 in the clinical expression of AD neuropathologic change. This proposal will address the hypotheses that tau and TDP-43 synergize to drive neurodegeneration and that targeting both toxic proteins may have stronger protective effects than targeting either alone. The project builds on Dr. Latimer’s previous work with Drs. Kraemer and Liachko demonstrating the synergism between tau and TDP-43 in a C. elegans model of combined proteotoxicity, and autopsy data in the Adult Changes in Thought (ACT) study, a unique, longitudinal community-based cohort of older adults recruited from the Seattle area, in which TDP-43 pathology is associated with dementia and increased pathologic tau. Dr. Latimer will test known genetic modifiers of tau or TDP-43 neurotoxicity in the tau/TDP-43 C. elegans model (Aim 1) and determine whether TDP-43 and tau pathology correlate in human brain tissue, leveraging data from the ACT autopsy cohort (Aim 2). She will then use neuropathology data to select cases for RNA-Seq analysis in the ACT cohort to identify novel modifiers of tau and TDP-43 proteotoxicity that can be biologically validated in the tau/TDP-43 C. elegans model (Aim 3). Completion of the aims will set the stage for future independent funding using human genetic and neuropathologic data coupled with C. elegans models and lay the foundation for a new generation of AD therapeutics that can be further evaluated in other cohorts and model systems.


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 = -$277 )
2025	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Aging Research	000	5	4/28/2025	NON-COMPETING CONTINUATION	-$277
														Subtotal = -$277

Issue Date FY: 2024 ( Subtotal = $141,441 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Aging Research	000	5	1/23/2024	NON-COMPETING CONTINUATION	$141,441
														Subtotal = $141,441

Issue Date FY: 2023 ( Subtotal = $140,780 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Aging Research	000	4	2/2/2023	NON-COMPETING CONTINUATION	$140,780
														Subtotal = $140,780

Issue Date FY: 2022 ( Subtotal = $140,679 )
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Aging Research	000	3	4/22/2022	NON-COMPETING CONTINUATION	$140,679
														Subtotal = $140,679

Issue Date FY: 2021 ( Subtotal = $140,697 )
2021	2021	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Aging Research	000	2	2/5/2021	NON-COMPETING CONTINUATION	$140,697
														Subtotal = $140,697

Issue Date FY: 2020 ( Subtotal = $141,834 )
2020	2020	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Aging Research	000	1	1/10/2020	NEW	$141,834
														Subtotal = $141,834

Grand Total All Awards = $705,154

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Molecular Mechanisms of Synergistic TDP-43 and Tau Proteotoxicity in Alzheimer's Disease

Award Number: K08AG065426

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/15/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer