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Abstract Details

CSF aSyn-SAA and Alzheimer's Disease Biomarkers: Presentation and Progression in the Dementia with Lewy Bodies Consortium
Aging, Dementia, and Behavioral Neurology
P7 - Poster Session 7 (5:00 PM-6:00 PM)
3-011

To explore association of CSF alpha-synuclein seed amplification (αSyn-SAA) and CSF Alzheimer’s disease (AD) biomarker profiles with presenting features and longitudinal decline in the multicentered prospective Dementia with Lewy Bodies (DLB) Consortium study.

αSyn-SAA accurately detects αSyn pathology in synucleinopathies including DLB. AD co-pathology occurs in ~70% of DLB participants at autopsy and can be detected using CSF markers. The association of different αSyn/AD biomarker profiles with clinical outcomes in DLB can aid prognostication and inform clinical trial design.

CSF samples obtained <1 year of baseline assessments from participants of the DLB consortium study were analyzed for αSyn-SAA (Amprion SynTap assay), Aβ42/40, ptau-181, and total-tau (Luminex-xMAP technology; Millipore). Cut-points were defined as per Jain et al. Alzheimers Dement. 2024.  Cross-sectional comparisons of core DLB features, cognitive impairment, and hyposmia (<15th percentile of predicted performance) in participants with different CSF biomarker profiles was performed. Rates of cognitive decline, measured by MoCA scores, and motor decline, measured by MDS-UPDRS scores, were assessed.

Ninety-five participants with CSF αSyn-SAA and AD biomarkers were studied; 69% (66/95) were αSyn-SAA+.  αSyn-SAA+ participants had worse baseline MoCA scores (p=0.02), worse motor parkinsonism (p=0.003), were more likely to be hyposmic (p<0.0001), and had more core DLB features (p=0.04). Of αSyn-SAA+ participants, 41% (27) had normal AD biomarkers (Aβ42/40, ptau181, t-tau all normal), and 53% (35) had evidence of Amyloid-β co-pathology (Aβ42/40 abnormal, ±p-tau181, ±t-tau)  αSyn-SAA+ participants had greater progression in cognitive deficits and parkinsonism than αSyn-SAA- participants (MoCA Coefficient=-0.77, p=0.029. MDS-UPDRSpartIII Coefficient 3.54, p<0.0001).  αSyn-SAA+Aβ+ participants had greater declines in MoCA scores than αSyn-SAA+Aβ- participants (Coefficient=-1.98, p<0.0001).  MDS-UPDRSpartI subscores increased more in αSyn-SAA+Aβ+ participants than in αSyn-SAA+Aβ- participants (Coefficient=1.86, p=0.02).

 In this well-characterized cohort of DLB participants, αSyn-SAA positivity is associated with greater motor and cognitive decline. AD co-pathology is common and confers additional risk of cognitive decline.
Authors/Disclosures
David G. Coughlin, MD (University of California San Diego)
PRESENTER 		Dr. Coughlin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for M3 Global Research. The institution of Dr. Coughlin has received research support from 好色先生. The institution of Dr. Coughlin has received research support from NIA. The institution of Dr. Coughlin has received research support from NINDS.
Lavanya Jain (Cleveland Clinic) No disclosure on file
Maria Khrestian (Cleveland Clinic) No disclosure on file
Karen MacLeod, BA Ms. MacLeod has received personal compensation for serving as an employee of Amprion Inc..
Andrea Bozoki, MD, FAAN (University of North Carolina) Dr. Bozoki has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Creative Biopeptides. Dr. Bozoki has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cognition Therapeutics. The institution of Dr. Bozoki has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AviadoBio. The institution of Dr. Bozoki has received research support from Cognition Therapeutics. The institution of Dr. Bozoki has received research support from EIP Pharma. The institution of Dr. Bozoki has received research support from Transposon Therapeutics. The institution of Dr. Bozoki has received research support from Alector .
James E. Galvin, MD, MPH (University of Miami Miller School of Medicine) Dr. Galvin has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Cognivue. Dr. Galvin has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Biogen. Dr. Galvin has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eisai. Dr. Galvin has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Galvin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GE Healthcare. Dr. Galvin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Galvin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PassageBio. The institution of Dr. Galvin has received research support from National Institutes of Health. Dr. Galvin has received intellectual property interests from a discovery or technology relating to health care. Dr. Galvin has a non-compensated relationship as a Board of Directors with Alzheimer Association Southeast Florida Chapter that is relevant to AAN interests or activities. Dr. Galvin has a non-compensated relationship as a Board of Directors with Lewy Body Dementia Association that is relevant to AAN interests or activities. Dr. Galvin has a non-compensated relationship as a Board of Directors with Lewy Body Dementia Resource Center that is relevant to AAN interests or activities.
David Irwin, MD (University of Pennsylvania) The institution of Dr. Irwin has received research support from NIH. The institution of Dr. Irwin has received research support from Prevail. The institution of Dr. Irwin has received research support from Passage Bio. The institution of Dr. Irwin has received research support from Alector. The institution of Dr. Irwin has received research support from Transposon. The institution of Dr. Irwin has received research support from Denali. The institution of Dr. Irwin has received research support from Cervo Med.
Carol F. Lippa, MD (Thomas Jefferson University) Dr. Lippa has nothing to disclose.
Irene Litvan, MD, FAAN (UC San Diego Parkinson and Other Movement Disorder Center) Dr. Litvan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aprinoia. Dr. Litvan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Litvan has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology. Dr. Litvan has received personal compensation in the range of $50,000-$99,999 for serving as a Chief Editor with Frontiers in Neurology.
Oscar L. Lopez, MD, FAAN Dr. Lopez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acumen.
Sarah Berman, MD (University of Pittsburgh) The institution of Dr. Berman has received research support from NIH.
Debby W. Tsuang, MD (VAMC 116 MHC) Dr. Tsuang has nothing to disclose.
Cyrus P. Zabetian, MD (VA Puget Sound Health Care System) The institution of Dr. Zabetian has received research support from American Parkinson Disease Association. The institution of Dr. Zabetian has received research support from Department of Veterans Affairs. The institution of Dr. Zabetian has received research support from NIH. Dr. Zabetian has a non-compensated relationship as a Member, Scientific Advisory Council with Lewy Body Dementia Association that is relevant to AAN interests or activities.
Jori Fleisher, MD, MSCE, FAAN (Rush University Parkinson's and Movement Disorders Program) The institution of Dr. Fleisher has received research support from Parkinson's Foundation. The institution of Dr. Fleisher has received research support from NIH/NINDS. The institution of Dr. Fleisher has received research support from NIH/NINDS. The institution of Dr. Fleisher has received research support from NIA/NINDS. The institution of Dr. Fleisher has received research support from NIA/NINDS. Dr. Fleisher has received publishing royalties from a publication relating to health care. Dr. Fleisher has received personal compensation in the range of $0-$499 for serving as a Speaker with Parkinson's Foundation. Dr. Fleisher has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Lewy Body Dementia Association. Dr. Fleisher has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Davis Phinney Foundation. Dr. Fleisher has a non-compensated relationship as a Editorial Board Member with AAN Brain & Life Magazine that is relevant to AAN interests or activities.
Angela Taylor (Lewy Body Dementia Association) Mrs. Taylor has received personal compensation for serving as an employee of Lewy Body Dementia Association.
James B. Leverenz, MD, FAAN (Cleveland Clinic) Dr. Leverenz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Leverenz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Leverenz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai.
Lynn Bekris (Cleveland Clinic) No disclosure on file
Douglas Galasko, MD (Dept. of Neurosciences, UCSD) Dr. Galasko has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Galasko has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly, Inc. Dr. Galasko has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Diagnostics. Dr. Galasko has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cognition THeraprutics. Dr. Galasko has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Artery Therapeutics.