LBD: Understand LBD genetic, epigenetic, and environmental influences (Milestone 1.L)
Timeline Start - End2016 - 2027
Research Implementation AreaPopulation Studies and Precision Medicine
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.
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.
- 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)
Research Programs and Resources
- 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
- 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)