Accelerating Medicines Partnership – Alzheimer's Disease Phase 2

The Problem
Slow progress in the Alzheimer’s disease therapeutic arena is attributed to insufficient understanding of the complex biology and heterogeneity of the disease process.
The Solution
AMP AD will enable precision medicine research for Alzheimer’s disease that will accelerate the development of therapies though deep and longitudinal molecular analyses across diverse populations.

Overview

The Accelerating Medicines Partnership Alzheimer’s Disease (AMP AD Phase 2)  is a new precompetitive public-private partnership that will enable precision medicine research for Alzheimer’s Disease through deep and longitudinal molecular analyses across diverse populations to provide insights that will accelerate the development of therapies for Alzheimer’s Disease. 

This multisector partnership, managed by the Foundation for the NIH, will focus on providing a data-driven approach for identification and validation of biomarkers that will lead to increased clinical trial success.

AMP AD Phase 2 builds on the success of AMP AD Phase 1 and  joins five other AMP programs, which are all coordinated by the FNIH, that use cutting-edge scientific approaches to bring new medicines and supports to patients by enhancing validation of novel, clinically relevant therapeutic targets and biomarkers. Click here to learn more about AMP in general. To learn about AMP Type 2 Diabetes click here, AMP RA/SLE Project click here, AMP Parkinson's Disease click here, or AMP Schizophrenia click here.

Read the National Institute on Aging’s (NIA’s) description of the program here.

Partners

Public-Sector Partners:

  • National Institute of Neurological Disorders and Stroke (NINDS)
  • National Institute on Aging (NIA)*
  • U.S. Food and Drug Administration (FDA)

Private-Sector Partners:

  • Alzheimer's Association®*
  • Gates Ventures*
  • Eisai Inc. *
  • GlaxoSmithKline plc (GSK)*
  • Takeda Pharmaceutical Company Limited*

*Provided financial support for this program.

FNIH Contact

  • Eline Appelmans, M.D., MPH, BMedSci, Scientific Program Manager, Neuroscience, Research Partnerships, eappelmans@fnih.org

About Alzheimer’s Disease

Alzheimer's Disease is projected to affect approximately 14 million people by the year 2060.  Alzheimer’s is a progressive brain disorder that is the most common cause of dementia in older adults. Dementia is the loss of thinking, remembering and reasoning abilities (neuro cognitive functions) to the extent that it interferes with a person’s daily life and activities. It is not a normal part of aging and has many potential causes. Alzheimer’s Disease is characterized by changes in the brain called amyloid plaques and tau tangles as well as a loss of connections between nerve cells (neurons) in the brain. Neurons transmit messages between different parts of the brain, and from the brain to muscles and organs in the body. AMP AD works to further unravel the complex molecular changes involved in Alzheimer’s Disease to speed up identification of novel drug targets. For more information on Alzheimer’s Disease and related dementia’s click here.

Need for New Therapies

Despite substantial investment in Alzheimer's Disease research, the treatment options available today only temporarily improve symptoms without stopping the underlying decline and death of brain cells. Given the extremely high failure rate for investigative Alzheimer’s treatments – nearly 100 percent – this field needs innovations like AMP AD to enable an understanding of the complex biology and heterogeneity of the disease process.

Approach

AMP AD will considerably enhance and further transform Alzheimer’s research by:  

  • Identifying and validating new targets and biomarkers. Discovering targets and biomarkers associated with different molecular subtypes of the disease will enable drug developers to select the right populations of patients for targeted treatments in clinical trials.
  • Expanding and refining understanding of disease pathway. AMP AD will support enhanced efforts to map Alzheimer’s Disease progression on a cellular and molecular level and will increase the availability of longitudinal data, giving researchers a more detailed and dynamic understanding of the disease that may open the door to new treatment approaches. 
  • Increasing access to de-identified data from racially and ethnically diverse cohorts. Too often, research on Alzheimer’s does not reflect the diversity of the populations affected by the disease. In its next phase, AMP AD will help address this gap by diversifying the dataset that is available through its centralized knowledge portal, prioritizing the addition of information from populations most at risk, including Black and Latinx, to enable a precision medicine approach.
  • Enhancing data-sharing capabilities of existing centralized data repository and knowledgebase. AMP AD will continue to make all the individual subject-level data it generates available to researchers worldwide for use in  basic research and therapy development through the NIA’s access controlled AD Knowledge Portal as well as analytical outputs and target nominations through the open-source platform, Agora. The AD Portal and Agora are expected to roll out new technologies that make it easier to share and access critical data, increasing the project’s impact and value to partners.

Media

FNIH Press Release (March 2021): Foundation for the NIH announces Alzheimer’s Disease research initiative to accelerate progress on treatments

NIA Press Release (March 2021): NIH reinvests in transformative public-private partnership to advance precision medicine research for Alzheimer’s Disease

Scientific Publications

Over 200 publications based on AMP AD datasets, to explore publications click here. Recent:

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture – Nature Genetics

The role of RHOT1 and RHOT2 genetic variation on Parkinson disease risk and onset  Science Direct

Meta-Analysis of the Alzheimer's Disease Human Brain Transcriptome and Functional Dissection in Mouse ModelsCell Reports

Molecular estimation of neurodegeneration pseudotime in older brainsNature Communications

Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer’s diseaseScience Advances

Large-scale proteomic analysis of Alzheimer's disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activationNature Medicine 

Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolomeNature Communications

Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer's disease  – Nature Communications

Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer’s DiseaseCell Reports

Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s diseaseNature Communications

Deciphering cellular transcriptional alterations in Alzheimer's disease brainsMolecular Neurodegeneration

Multiscale causal networks identify VGF as a key regulator of Alzheimer’s diseaseNature Communications

Transformative Network Modeling of Multi-1 Omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for ADNeuron 

AMP AD Knowledge Portal

Click here to discover and download Alzheimer's Disease data, analyses, and tools from AMP AD.

AMP AD Agora Platform

Agora is an open-source platform, created to provide curated AMP AD verified systems biology analyses showing which genes are associated with Alzheimer's Disease (AD).  Click here to learn more.

Support

The FNIH has raised a total of $13.45 million in private- sector partner contributions to fund this new 5-year AMP AD endeavor. This seeks to leverage NIA contribution of over $61.4 million, bringing the total combined public and private sector commitment to over $74.85 million over five years. The new AMP AD involves government, industry, private offices  and not-for-profit research, advocacy and care organizations in a collaboration that will advance Alzheimer’s Disease research on a scale that would not otherwise be possible.