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Continue to support cross-disciplinary research to discover and understand disease mechanisms that are common between AD and other neurodegenerative disorders including rare disorders and leverage these for therapy development. These efforts should include discovering new pathways leading to synaptic and neural damage understanding the structural variations of pathogenic peptides collected from well-phenotyped, diverse cohorts to inform the design of structure-specific imaging agents and inhibitors with therapeutic potential.
2028 PAS-17-028: Common Mechanisms and Interactions Among Neurodegenerative Diseases (R01) PAR-18-596: Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01) NOT-AG-18-001 (#3): in vivo Synaptic Function in Alzheimer's Disease and Related Dementias RFA-AA-18-007: NIH Blueprint for Neuroscience Research: Dynamic Neuroimmune Interactions in the Transition from Normal CNS Function to Disorders (R01) RFA-AG-18-023: Pathogenesis of Age-related HIV Neurodegeneration (R01) RFA-AG-18-025: Consequences of amyloid protein polymorphisms in Alzheimer's disease (R01) PAR-15-357: Understanding Alzheimer's Disease in the Context of the Aging Brain (R01)-2 funded grants PAR-15-358 : Capturing Complexity in the Molecular and Cellular Mechanisms Involved in the Etiology of Alzheimer’s Disease (R01) PAR-19-070: Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) PAR-19-071: Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) RFA-AG-20-028: Implementation Research on Hypertension Control to Prevent Dementia and Cognitive Decline (R61/R33 Clinical Trial Optional) RFA-AG-21-006: Alzheimer’s Disease Sequencing Project Functional Genomics Consortium (U01 Clinical Trial Not Allowed) RFA-AG-22-030: Resource Networks for Protein Polymorphisms in Alzheimer’s Disease and its Related Dementias (AD/ADRD) (U24 Clinical Trial Not Allowed) RFA-AG-25-024: Access and Manipulation of Brain Cell Subtypes Implicated in Aging and AD/ADRD (R61/R33 Clinical Trial Not allowed) 2.H In Progress Continue to support cross-disciplinary research to discover and understand disease mechanisms... DN 2018 AD Summit: 1H, 4M and 7H Workshop: Disruptive Approaches to Understand the Initiation and Transmission of Misfolded Proteins in Alzheimer’s Disease News: Faulty protein connections short-circuit brain in Alzheimer's disease Workshop: HIV and Aging Related Neurodegeneration, November 9-10, 2020, virtual News: Different forms of tau protein may relate to how fast dementia worsens Amyloid structure linked to different types of Alzheimer’s disease TREM2 protein seems to protect brain cells from toxic TDP-43 protein Workshop: Cell-Specific Proteome Dynamics and Biomolecule Imaging in Brain Aging and Alzheimer’s Disease: Bridging the Gap From Basic to Clinical Proteomics Workshop: Olfactory Dysfunction in Aging and Neurodegenerative Disease Workshop: Current Progress and New Directions in Delirium Research Workshop: Molecular Mechanisms and Pathobiology of TDP-43 in LATE and Alzheimer's Disease and Its Related Dementias Research on Disease Mechanisms NIH Blueprint for Neuroscience Research Common Mechanisms and Interactions Among Neurodegenerative Diseases (R01)
- Identify and preclinically validate at least three novel therapeutic targets that are common to AD and at least two other neurodegenerative disorders.
- Launch a minimum of three drug discovery projects targeting pathways common across AD at least two other neurodegenerative disorders.
Summary of Key Accomplishments
NIA supports research aimed at understanding disease mechanisms that are shared between AD and other neurodegenerative disorders. For example, NIA supports several ongoing projects supported through a targeted funding initiative are investigating the shared mechanisms among AD, Parkinson’s, Lewy body dementia, and Huntington’s disease, to identify novel shared targets for multiple disorders.
In 2021, NIA established the Protein Polymorphism Resource Network to standardize procedures to isolate and characterize tau aggregates and fibrils—abnormal accumulations of protein observed in AD and several other neurodegenerative disorders—across the AD/ADRD and neurodegenerative disease research communities. For example, the network has already made AD-derived tau filaments available for researchers. NIA also launched a funding opportunity to elucidate the roles of transposable elements—portions of genetic material that can change position within the genome and have been implicated in a range of neurodegenerative diseases—in AD/ADRD and aging. A project funded under this initiative aims to combine human cell-based models and postmortem tissues from AD and FTD patients to study the relationship between transposable elements and TDP-43, a protein often observed in abnormal accumulations in AD, FTD, and other neurodegenerative diseases.
In April 2024, NIA hosted a workshop focused on molecular mechanisms and pathobiology of TAR DNA-binding protein 43 (TDP-43) in limbic predominant age-related TDP-43 encephalopathy (LATE) and AD. The workshop audience included researchers interested in this field and aimed to fill in the gaps in understanding mislocalization and dysfunction of TDP-43. It addressed the mechanisms of TDP-43 aggregation and propagation in LATE and AD and identified the critical events for maintenance of TDP-43 functions and brain health.
The key accomplishments summary is current as of September 2025.