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Abstract Details

The Syn-D Study: Detection of Longitudinal Changes in Cutaneous Phosphorylated Alpha-Synuclein in Mild Cognitive Impairment
Aging, Dementia, and Behavioral Neurology
S42 - Perspectives on Non-Alzheimer's Dementia Diagnostics and Therapeutics (2:48 PM-3:00 PM)
010

To quantify cutaneous phosphorylated alpha-synuclein (P-SYN) deposition in patients with mild cognitive impairment (MCI) due to suspected Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB).

Quantitative assessment of P-SYN using skin biopsies can facilitate the diagnosis of complex neurological disorders and serve as a potential therapeutic biomarker in clinical trials. We sought to validate a reproducible marker of synuclein pathology in patients with MCI with DLB phenotype (MCI-DLB) and MCI AD phenotype (MCI-AD).

After consent, participants with MCI-AD and MCI-DLB completed neurological examinations, medical history screening, and motor assessments. An expert panel blinded to pathology reviewed clinical assessments to confirm diagnoses. Distal leg, distal thigh, and posterior cervical skin biopsies were performed with quantitation of P-SYN.

103 MCI patients were enrolled, with 98 confirmed by expert panel to meet inclusion criteria. Of these, 44 were MCI-DLB (73.3±8.3 years, 11 female), 35 were MCI-AD (73.0±5.1, 18 female), and 19 were MCI-indeterminate (MCI-ind; 67.8 ± 10.0, 8 female). Groups did not differ in demographics or baseline Clinical Dementia Rating (CDR 0.5 for all groups).  At time of abstract submission, follow-up data were available for 71 patients (33 MCI-DLB, 26 MCI-AD, and 12 MCI-ind).  At follow-up, P-SYN was detected in 85% of MCI-DLB and 41% of MCI-AD patients.  A continuous measure of total P-SYN increased in 69.7% of MCI-DLB, 15.3% of MCI-AD, and 25% of MCI-ind.  Across groups, there was a statistically significant increase in P-SYN over 12 months (p<0.001), which was greater for MCI-DLB compared to MCI-AD (p<0.001) and significantly predicted increases in CDR sum of boxes (p=0.008).
Cutaneous P-SYN is detected in most patients with MCI-DLB.  The prevalence in MCI-AD is consistent with autopsy reports of co-pathology.  P-SYN deposition correlates with declines in cognitive function observed in MCI. Rate of cutaneous P-SYN increases may distinguish between dementia subtype trajectories. 
Authors/Disclosures
Roy L. Freeman, MD (Beth Israel Deaconess Hosp)
PRESENTER 		Dr. Freeman has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Cutaneous Diagnostic Life Sciences. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vertex. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Theravance. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Inhibikase. Dr. Freeman 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 Elsevier. The institution of Dr. Freeman has received research support from NIH. The institution of Dr. Freeman has received research support from Theravance. The institution of Dr. Freeman has received research support from Biohaven. The institution of Dr. Freeman has received research support from Lundbeck. Dr. Freeman has received research support from Regeneron.
Todd D. Levine, MD (Honor Health) Dr. Levine has received personal compensation for serving as an employee of CND life sciences . Dr. Levine has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Nufactor. Dr. Levine has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for PNA. Dr. Levine has or had stock in CND Life Sciences.Dr. Levine has or had stock in Corinthian reference lab.
Bailey Bellaire (CND Life Sciences) Bailey Bellaire has received personal compensation for serving as an employee of CND Life Sciences.
Jourdan Parent, PhD Dr. Parent has received personal compensation for serving as an employee of CND Life Sciences.
Sarrah Marcotte Miss Marcotte has received personal compensation for serving as an employee of CND Life Sciences.
Manuel X. Duval, PhD Mr. Duval has received personal compensation for serving as an employee of CND Life sciences.
Christopher H. Gibbons, MD, FAAN (Beth Israel Deaconess Medical Center) Dr. Gibbons has received personal compensation for serving as an employee of CND Life Sciences. Dr. Gibbons has or had stock in CND Life Sciences.Dr. Gibbons has received publishing royalties from a publication relating to health care.