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Abstract Details

Identification of CSF Biomarkers of Cognitive Impairment and Cerebellar Dysfunction in Multiple Sclerosis
MS and Related Diseases
P03 - (-)
230
BACKGROUND: Patients with MS who have significant cognitive impairment often have associated cerebellar dysfunction and these symptoms are typically refractory to treatment. The underlying pathophysiology behind this symptom complex is poorly understood. Predictive biomarkers of this symptom complex may allow for early therapeutic interevention.
DESIGN/METHODS: CSF samples were obtained from MS patients with or without co-existing cerebellar dysfunction and cognition impairment, which were determined by neurological exam and cognitive screening test battery, respectively. Candidate biomarkers were identified by mass spectrometry-based MRM technology (NextGen Sciences) which simultaneously quantifies 82 proteins in CSF. Biomarkers were validated in CSF by ELISA and Luminex assays. Results were normalized for CSF protein content by BCA assay, and analyzed for statistical significance using the Student's T test.
RESULTS: 17 of the 82 proteins analyzed by mass spectrometry showed a statistically significant concentration difference in the CSF of MS patients with cognitive/cerebellar dysfunction (n=5) compared to those without (n=5). Candidate proteins were then validated using CSF from a larger cohort of patients with (n=20) and without (n=17) cognitive/cerebellar dysfunction. Upon validation, there was a significant decrease in the CSF concentration of secreted APP (amyloid beta precursor protein) and APLP2 (amyloid beta precursor-like protein 2) in the cognitively impaired patient cohort compared to MS controls. To further analyze the role of the amyloid processing pathway in MS, we measured A?40, A?42, Tau, and pTau levels. CSF levels of Tau, pTau and A?40 were significantly lower in the cognitively impaired MS patients, whereas A?42 remained unchanged.
CONCLUSIONS: Our findings suggest that reduced levels of APP proteins in CSF may serve as useful biomarkers of cognition/cerebellar dysfunction in MS. Whether or not the APP pathway plays a pathological role in MS-related cognitive decline and cerebellar dysfunction remains to be determined.
Authors/Disclosures

PRESENTER 		No disclosure on file
Violaine K. Harris, PhD (Tisch Multiple Sclerosis Research Center of NY) No disclosure on file
No disclosure on file
Saud Sadiq, BS, FAAN (Tisch Multiple Sclerosis Research Center of New York) Ms. Brewi has nothing to disclose.
David Eidelberg, MD, FAAN (Feinstein Institute for Medical Research) Dr. Eidelberg has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for MeiraGTx. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TreeFrog Therapeutics. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Blue Rock Therapeutics, Inc.. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SANA Biotechnology, Inc. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bio Vie, Inc.. Dr. Eidelberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for KenaiTx, Inc.. Dr. Eidelberg has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aspen Neuroscience. Dr. Eidelberg has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Oxford University Press. The institution of Dr. Eidelberg has received research support from The Michael J. Fox Foundation for Parkinson's Research. The institution of Dr. Eidelberg has received research support from Lupus Research Alliance. The institution of Dr. Eidelberg has received research support from National Institutes of Health. The institution of Dr. Eidelberg has received research support from Blue Rock Therapeutics. The institution of Dr. Eidelberg has received research support from National Institute of Neurological Disorders and Stroke. The institution of Dr. Eidelberg has received research support from The Michael J. Fox Foundation for Parkinson's Research. The institution of Dr. Eidelberg has received research support from National Institute of Allergy and Infectious Diseases. The institution of Dr. Eidelberg has received research support from Aspen Neurosciences, Inc. . The institution of Dr. Eidelberg has received research support from NIH. Dr. Eidelberg has received intellectual property interests from a discovery or technology relating to health care. Dr. Eidelberg has received intellectual property interests from a discovery or technology relating to health care.