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AD-Related Dementias Focus
Identify overlapping pathogenic mechanisms between FTD and other neurodegenerative disorders and syndromes.
2029 PAR-22-023: Multi-Disciplinary Collaborations to Understand Mechanisms of Systemic Immune Signaling and Inflammation in ADRD and its Progression (R01 Clinical Trial Not Allowed) PAR-22-208: Structural Biology of Alzheimer's Disease Related Dementias (ADRDs) Proteinopathies (R01 Clinical Trial Not Allowed) PAR-23-211: Mechanistic Investigations into ADRD Multiple Etiology Dementias (R01 - Clinical Trial Not Allowed) PAR-23-212: Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD & other ADRDs (R01 - Clinical Trial Not Allowed) RFA-NS-24-001: Using Multimodal Biomarkers to Differentially Diagnose ADRDs for Clinical Trials (U19 Clinical Trial Optional) PAR-24-234: Mechanistic Investigations into ADRD Associated Protein Structures in Biological Settings (R01 - Clinical Trial Not Allowed) PAR-24-148: Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD and other ADRDs (R01 - Clinical Trial Not Allowed) 2.Z In Progress DN 2022 ADRD Summit: Frontotemporal Dementia, Milestone 4, Priority 4 Press Release: Abnormal proteins found in the spinal fluid of people with ALS and frontotemporal dementia Highlight: Abnormal proteins found in the spinal fluid of people with ALS and frontotemporal dementia Research on Disease Mechanisms Projects funded in FY22
- At least three studies to identify and compare overlapping molecular, genetic, clinical, and pathologic drivers and risk factors for FTD clinical outcomes with other AD/ADRD diagnoses.
Summary of Key Accomplishments:
Increasing evidence from NIH-funded research indicates a common pathogenic process may cause both FTD and ALS. Several FTD/ALS-linked proteins have been shown to have specific functions associated with a cellular structure, known as the endolysosome, that play a role in recycling materials within cells. One intriguing example is the lysosomal protein TMEM106b, which was recently discovered to form filaments in FTD, ALS and several other neurodegenerative disorders. Variants of TMEM106b are a risk factor for FTD, but its accumulation into filaments may be a common feature of the aging brain in general. TMEM106b’s role in aging and across a spectrum of neurodegenerative diseases remains an area of research focus.
In addition, NIH-funded researchers have identified a new type of fibril in the brains of people who died from a neurodegenerative condition called frontotemporal lobar degeneration with TDP-43 pathology. The fibril is composed of a fragment of a specific protein, genes for which have previously implicated as a genetic risk factor for this disease. The researchers also found this fibril in the brains of people who had died of other neurodegenerative conditions, such as dementia with Lewy bodies. Additional research is needed to better understand this role this fibril plays in neurodegenerative conditions.
The key accomplishments summary is current as of June 2024.