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

Studying the pathogenic roles of human CD8+ T cells in Alzheimer's disease using a 3D human Peripheral immune Chip.

Award Number: R01AG082328
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

Group Awards By:

View Award Description

Studying the pathogenic roles of human CD8+ T cells in Alzheimer's disease using a 3D human Peripheral immune Chip. - PROJECT SUMMARY Alzheimer’s disease (AD) is the leading cause of age-related dementia, in which neuroinflammation is highlighted to play a critical role in driving neurodegeneration. Emerging evidence has demonstrated crucial roles for peripheral immune cells in AD pathology by direct infiltration into brains and regulating brain-resident immune cells, including microglia. However, many critical questions remain unaddressed. Previously, our team developed a three-dimensional (3D) triculture model of AD with human microglia to study the interactions between microglia and AD neural cells. Although our 3D triculture model with microglial cells recapitulates robust neuroinflammation and neurodegeneration, it lacks another critical player in AD pathogenesis, peripheral immune cells. Therefore, we recently developed a unique 3D multicellular human Peripheral immune Chip (PiChip) model to overcome this limitation. This 3D neuroimmune axis model faithfully recapitulates AD pathology with innate and adaptive immune components. Our preliminary data from the PiChip model demonstrated a dramatic increase in the number of human T cells (but not B cells) selectively infiltrating into AD cultures versus control. Infiltration of CD8+ T cells into AD cultures led to microglial activation and it plays a critical role in exacerbating neuroinflammation and neurodegeneration in 3D AD PiChip models. In addition, we discovered key roles for the C-X-C motif chemokine ligand 10 (CXCL10) and its receptor, CXCR3, in regulating T-cell infiltration into AD cultures. Modulating this T cell CXCL10/CXCR3 signaling pathway largely prevented neuronal damage in AD neural-glial cultures. Based on these preliminary results, we proposed a comprehensive study underlying mechanisms of AD-specific T-cell recruitment, CD8+ T-cell mediated neural cell death, and their therapeutic implications, using 3D human cellular models, as well as relevant AD mouse models AD models. The overarching goal of this proposal is to use our unique multicellular PiChip system to gain a greater understanding of the crosstalk between CD8+ T cells and brain resident cells (mainly glial cells) in driving AD pathogenesis. We will achieve this goal by addressing the following aims: Aim 1. to study roles and therapeutic applications for blocking T-cell mediated neuronal deficits in AD; Aim 2. to study how CD8+ T cells trigger neurodegeneration via activating glial cells; Aim 3. to explore the roles of T cell activation and clonal expansion in AD pathogenesis. Successful completion of these aims will provide a better understanding of AD-specific mechanisms underlying the interaction of adaptive immune cells and brain resident cells in driving neurodegeneration, addressing a knowledge gap that promises to yield novel insights into better interventions and biomarkers.


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 = $686,998 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	001	3	2/26/2026	NON-COMPETING CONTINUATION	$68,699
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	000	3	1/28/2026	NON-COMPETING CONTINUATION	$618,299
														Subtotal = $686,998

Issue Date FY: 2025 ( Subtotal = $673,258 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	000	2	1/23/2025	NON-COMPETING CONTINUATION	$618,299
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	001	2	8/4/2025	NON-COMPETING CONTINUATION	$54,959
														Subtotal = $673,258

Issue Date FY: 2024 ( Subtotal = $688,000 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	000	1	3/27/2024	NEW	$688,000
														Subtotal = $688,000

Grand Total All Awards = $2,048,256

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Studying the pathogenic roles of human CD8+ T cells in Alzheimer's disease using a 3D human Peripheral immune Chip.

Award Number: R01AG082328

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer