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

Photocleavable Mass-Tags for Spatial Multiomics of Alzheimer’s Brain Tissue

Award Number: R44AG078097
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2025

Group Awards By:

View Award Description

Photocleavable Mass-Tags for Spatial Multiomics of Alzheimer’s Brain Tissue - Summary/Abstract Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by progressively worsening dementia. AD currently affects over 6.2 million persons in the U.S. and approximately 30 million world-wide with 70% over the age of 65. The total public health cost of AD is expected to reach over $20 trillion by 2050. Despite extensive efforts to develop AD therapies including small molecules, monoclonal antibodies and peptide-based drugs, only aducanumab, whose efficacy is in doubt, has been approved by the FDA since 2004. A major challenge is elucidating the molecular pathology involved in AD in order to develop effective early diagnostics and drugs. While amyloid plaque formation due to aggregation of different Aβ-peptides has been an important focus, a myriad of other molecules including tau, neuronal and glial receptors, endosomal-lysosomal related proteins, glycans, phospholipids, cholesterol and metabolites have also been implicated in AD pathology. In order to obtain a detailed understanding of the possible role of these diverse molecular species as well as the molecular targeting of candidate drugs, there is an urgent need to develop sufficiently powerful, highly multiplexed and multiomic tissue imaging techniques that can map at cellular resolution the 2D-spatial distribution and association of these diverse, AD molecular players. The proposed Phase II project seeks to address this challenge by applying a new highly- multiplexed, targeted method termed mass spectrometric imaging immunohistochemistry (MSI-IHC™). MSI- IHC™ is based on the use of novel photocleavable mass-tags (PC-MTs) developed by AmberGen which when linked to antibody or lectin probes enable targeted biomolecules to be identified in the mass spectrometric image. This approach significantly exceeds the multiplex capability of fluorescence immunohistochemistry (IHC) and previous cleavable mass-tag based methods which are generally limited to 5 biomarkers or require extensive cycling procedures in the case of fluorescence. In addition, the ability to combine MSI-IHC™ with label-free, untargeted small molecule mass spectrometric imaging (MSI) as well as fluorescence IHC imaging, on the same sample, greatly extends its power. This is possible using unique double-labeled fluorescent-PC-MT probes and performing 2 rounds of MSI. Together, these innovations can provide a much more comprehensive multiomic picture of the role of various molecules in AD pathology. In Phase I, we have demonstrated the feasibility of this approach on mouse and human brain tissue specimens including the ability to image simultaneously a variety of AD related molecules. In Phase II we will build on this progress by applying MSI-IHC™ to human and transgenic AD mouse brain tissue obtained from collaborators and commercial sources. One goal, in collaboration with Prof. R.A. Nixon at NYU, a leading AD researcher, will be to investigate the role of neuronal endosomal dysfunction, the earliest known pathobiology specific to AD. Image analysis with be performed using novel statistical physics and AI methods previously developed for AD tissue and brain imaging.


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 = $0 )
2026	2023	AMBERGEN, INC	44 MANNING RD	BILLERICA	MA	01821	MIDDLESEX	USA	Aging Research	000	2	1/27/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $1,081,032 )
2023	2023	AMBERGEN, INC	44 MANNING RD	BILLERICA	MA	01821	MIDDLESEX	USA	Aging Research	000	2	8/2/2023	NON-COMPETING CONTINUATION	$1,081,032
														Subtotal = $1,081,032

Issue Date FY: 2022 ( Subtotal = $1,354,952 )
2022	2022	AMBERGEN, INC	313 PLEASANT ST STE 4	WATERTOWN	MA	02472	MIDDLESEX	USA	Aging Research	000	1	8/15/2022	NEW	$1,354,952
														Subtotal = $1,354,952

Grand Total All Awards = $2,435,984

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Photocleavable Mass-Tags for Spatial Multiomics of Alzheimer’s Brain Tissue

Award Number: R44AG078097

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer