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AD-Related Dementias Focus
Delineate genetic loci and their functions contributing to the onset and progression of LBDs using genetic, transcriptomic, epigenetic, and environmental characterization analyses.
2027 PAR-17-054: Leveraging Existing Cohort Studies to Clarify Risk and Protective Factors for Alzheimer’s Disease and Related Dementias (R01) RFA-NS-20-014: Peripheral Pathology in the Lewy Body Dementias NOT-NS-21-001: Notice of Special Interest: Administrative Supplements for Connecting Pre-mortem Clinical Information with Post-Mortem Brain Analysis RFA-NS-21-006: Mechanisms of Pathological Spread of Abnormal Proteins in LBD and FTD RFA-NS-21-007: Mechanisms of Selective Vulnerability in LBD and FTD NOT-NS-21-037: Impact of COVID-19 on Dementia Risk, Progression and Outcomes in ADRD Populations PAR-22-048: Clinical Relevance of the Linkage between Environmental Toxicant Exposures and Alzheimer’s Disease and Related Dementias (R01 Clinical Trial Not Allowed) RFA-NS-23-017: Optimization of Genome Editing Therapeutics for Alzheimer's Disease and Alzheimer's Disease-Related Dementias (AD/ADRD) (U01 - Clinical Trials Not Allowed) PAR-23-211: Mechanistic Investigations into ADRD Multiple Etiology Dementias (R01 - Clinical Trial Not Allowed) PAR-24-249: Interaction Between Environmental Factors and Lewy Body Dementia (R01 - Clinical Trial Not Allowed) PAR-24-270: ADRD Risk and Disease Following Nervous System Exposures at Biological Interfaces with the Environment (R01 - Clinical Trial Not Allowed) 1.L In Progress Identify novel common and rare genetic variants, epigenetic changes, and environmental influences that impact the risk for and clinical features of LBD. 2016 ADRD Summit: Lewy Body Dementias (LBD) Focus Area 2: Discover Disease Mechanisms Through Brain Mapping and Genetics, Recommendation 4 (PDF, 901K) 2022 ADRD Summit: Lew Body Dementias (LBD) Milestone 5, Priority 1 (PDF, 3.4M) News: Genetic study of Lewy body dementia supports ties to Alzheimer’s and Parkinson’s diseases Population Studies and Precision Medicine NINDS Human Biomarkers Biospecimen and Data Repository (BioSEND) NINDS Human Cell and Data Repository (NHCDR) Parkinson’s Disease Biomarkers Program Consortium Meeting International Lewy Body Dementia Conference Accelerating Medicines Partnership in Parkinson’s Disease (AMP-PD) Select projects funded in FY21 Select projects funded in FY22 Gateway Exposome Coordinating Center Workshop: NASEM/CPOP Early Life Exposures Midlife Structural Solutions Workshop: The Future of Population-Based Studies in Alzheimer’s Disease and Related Dementia Research: Setting Future Scientific Priorities
- At least 2 new projects to identify new genomic changes and environmental influences that impact LBD.
- Discover a molecular mechanism that links at least one novel genetic locus to the risk for developing LBD.
Summary of Key Accomplishments
Recently, NIA/NINDS intramural staff led an international effort to sequence the genomes from 2591 individuals with LBD, and identified two new sites in the genome that are associated with risk for LBD. They also looked at risk genes that LBD shares with Parkinson's and AD and found differences between these disorders in how the shared risk genes were expressed. Another group of researchers looked at the DNA found in blood from individuals with the two LBD subtypes (Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD)) and found six locations where there were differences in how the DNA was externally modified. These changes were associated with worse cognitive symptoms in DLB and more REM behavior disorders in PDD, respectively.
The key accomplishments summary is current as of July 2022.