Abstract Details

Title Autopsy Validation of Biomarker-derived Biological Classifications in Lewy Body Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 13-011

Objective To evaluate biomarker-based classifications for Lewy body disease (LBD) including synuclein pathology (S), nigral degeneration (N), and genetic risk against autopsy-confirmed pathology in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).

Background Analogous to the ATN framework in Alzheimer’s disease (AD), advances in α-synuclein biomarkers have led to proposals for biologically based LBD classifications (SynNeurGe and neuronal α-synuclein disease [NSD]).

Design/Methods We analyzed 168 autopsied LBD cases from AZSAND with postmortem CSF synuclein seed amplification assay (SAA) results. SAA status (S+/S-) was compared to Lewy body (LB) pathology. Substantia nigra (SN) pigmented neuronal loss score (0-3) served as proxy for dopaminergic neuronal degeneration, with scores >0 considered N+. We also evaluated stricter cutoffs (>1 or >2) to approximate neuroimaging-based anchors.

Results

Of 168 LBD cases, 149 were S+, 19 S-. S+ cases were younger (84.2 vs 89.7 years, p=0.004), more functionally impaired (Unified Parkinsons Disease Rating Scale-II 14.2 vs 6.6, p=0.006), and had more frequent RBD (41.6% vs 5.3%, p<0.001). S+ cases had higher Unified Staging System for Lewy body disorders stage, LB density, and SN neuronal loss (p<0.001). All PD (n=71) and DLB (n=28) were S+, as were 26/32 incidental LBD (ILBD) and 21/30 AD with Lewy bodies (ADLB). Using SN score >0 as N?, S+N+ cases included all PD (n=71), 25/28 DLB, 9/26 ILBD, and 9/21 ADLB. Using SN score >1, these decreased to 67/71 PD, 17/28 DLB, 4/26 ILBD, and 1/21 ADLB. At SN>2, S+N+ cases were 55/71 PD, 9/28 DLB, 2/26 ILBD, and 0/21 ADLB.

Conclusions Using pathology-based N+ definitions, SynNeurGe and NSD classifications were validated in autopsy-confirmed PD and most DLB. ILBD and ADLB encompassed both S?N? and S?N? cases, reflecting prodromal and transitional LBD states. The optimal pathology-based threshold for N? corresponding to imaging positivity remains to be defined.

Authors/Disclosures
Shannon Y. Chiu, MD, MSc (Mayo Clinic Arizona) PRESENTER	Dr. Chiu has received research support from NIH.
Parichita Choudhury, MD (Banner Sun Health Research Institute)	The institution of Dr. Choudhury has received research support from Lewy Body Dementia Association. The institution of Dr. Choudhury has received research support from Arizona Alzheimer's Consortium.
Cecilia Tremblay (Banner Sun Health Research Institute)	Cecilia Tremblay has nothing to disclose.
Abdirahim Aden, MBChB (Mayo Clinic)	Dr. Aden has nothing to disclose.
Holly A. Shill, MD, FAAN (Barrow Neurology Clinics)	Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Biogen. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KeifeRx. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis Precision Medicine. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fasikl Inc. Dr. Shill has received personal compensation in the range of $0-$499 for serving as a Consultant for Boston Scientific. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe Pharma America.
Erika Driver-Dunckley, MD, FAAN	Dr. Driver-Dunckley has nothing to disclose.
Shyamal Mehta, MD, PhD, FAAN (Mayo Clinic, Arizona)	Dr. Mehta has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Adamas Pharma. Dr. Mehta has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. Dr. Mehta has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CNS Ratings.
Andrea Mastrangelo, MD (Università di Bologna)	Dr. Mastrangelo has nothing to disclose.
Piero Parchi, MD, PhD (Alma Mater Studiorum, University of Bologna)	The institution of Dr. Parchi has received research support from Ministero della Salute, ITA. The institution of Dr. Parchi has received research support from Ministero della Ricerca. The institution of Dr. Parchi has received research support from Ministero della Salute.
Christine Belden	Christine Belden has nothing to disclose.
Geidy Serrano	Geidy Serrano has nothing to disclose.
Thomas Beach (Banner Sun Health Research Institute)	Thomas Beach has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vivid Genomics. Thomas Beach has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Diagnostics. The institution of Thomas Beach has received research support from National Institutes of Health. The institution of Thomas Beach has received research support from Michael J Fox Foundation . The institution of Thomas Beach has received research support from State of Arizona.
Charles H. Adler, MD, PhD, FAAN (Mayo Clinic Arizona)	Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Adler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CND Life Sci. Dr. Adler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jazz. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precon. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. The institution of Dr. Adler has received research support from NIH. The institution of Dr. Adler has received research support from Michael J. Fox Foundation. The institution of Dr. Adler has received research support from Arizona Biomedical Research Commission. Dr. Adler has received publishing royalties from a publication relating to health care.

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