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AD-Related Dementias Focus
Develop and refine biomarkers for diagnosis, prediction, and prognosis utilizing biofluids, tissues, and digital and electrophysiological methods.
2027 RFA-NS-16-022: Biomarkers for the Lewy Body Dementias (U01) RFA-NS-17-016: Leveraging Existing Resources for Research on Lewy Body Dementia (R03 PAR-19-170: Progression Markers for Cognitive Impairment in Parkinson's Disease Dementia (R01) RFA-NS-19-014: Center without Walls for PET Ligand Development for Alzheimer's disease related dementias (ADRDs) (U19) 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-22-001: Biomarkers for the Lewy Body Dementias (U01 Clinical Trial Not Allowed) RFA-NS-22-062: Connecting Machine Readable Digital Human AD/ADRD Neuropathological Library Platforms for Advanced Analytics (U24 Clinical Trial Not Allowed) RFA-NS-24-001: Using Multimodal Biomarkers to Differentially Diagnose ADRDs for Clinical Trials (U19 Clinical Trial Optional) RFA-NS-24-026: Validating digital health technologies for monitoring biomarkers in ADRD clinical trials (R61/R33 - Clinical Trials Optional) 9.P In Progress LBD biomarker development DN 2016 ADRD Summit: Lewy Body Dementias (LBD) Focus Area 3: Develop and Validate Biological and Imaging Biomarkers, Recommendation 6 2022 ADRD Summit: Lewy Body Dementias (LBD) Milestone 3, Priority 3 Workshop: Advancing Digital Endpoints & Digital Health Technologies for Neurological and Neuromuscular Disorders Workshop: Dementia with Lewy Bodies: Filling the Gaps in Translational and Clinical Research Progression Markers for Cognitive Impairment in Parkinson's Disease Dementia (R01) Center without Walls for PET Ligand Development for Alzheimer's disease related dementias (ADRDs) (U19) NINDS Parkinson’s Disease Biomarkers Program (PDBP) NIH NeuroBioBank NINDS BioSEND NINDS Human Cell and Data Repository (NHCDR) Select projects funded in FY21 Select projects funded in FY22
- At least one clinical trial ready validated LBD biomarker that uses biofluids, tissues, digital or electrophysiological approaches (or a combination of approaches) for LBD diagnosis, prediction, and/or prognosis.
Summary of Key Accomplishments
The NINDS Parkinson’s Disease Biomarker Program (PDBP) supports several investigations focused on developing biomarkers for LBD, including neuroimaging, blood, cerebrospinal fluid (CSF), and proteomic biomarkers. One promising biomarker for LBD is the alpha-synuclein seeding assay. However, the commercially available version of this assay is invasive, requiring cerebrospinal fluid obtained by lumbar puncture. NIH is funding multiple studies to improve the existing assay as well as develop new versions that use other types of specimens, such as skin or nasal brushings, to make the assay less invasive and easier to use. A group of NIH-funded researchers recently demonstrated that their version of the assay can successfully differentiate individuals with DLB from individuals with Parkinson's disease, even though both disorders develop abnormal alpha-synuclein deposits in the brain.
Other biomarker types are in development. One small NIH-funded study showed that EEG patterns (a measure of brain electrical activity) were significantly different in LBD subjects than in subjects with Parkinson’s or Alzheimer’s, while a separate team of NIH-funded investigators used unique EEG patterns to identify cognitive impairment in subjects with Parkinson’s before they were diagnosed with Parkinson’s disease dementia. Another NIH-supported study used a large neuroimaging (MRI) database and a machine learning algorithm to differentiate among people with Alzheimer’s, DLB, FTD and normal controls based on the white matter connections in their brains. People with DLB were distinguished from the other groups by their unusual motor connections. Researchers have also shown that higher blood levels of a particular protein known as neurofilament light chain predicted which individuals with Parkinson’s would go on to develop Parkinson’s with dementia (PDD). In addition, researchers recently developed a distinct 7-protein expression profile that can distinguish DLB patients from AD patients.
Finally, both alpha-synuclein and neurofilament light chain biomarker assays are being performed in a large, longitudinal study to determine if they are associated with progression from REM sleep behavior disorder to LBD.
The key accomplishments summary is current as of July 2024.