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Abstract Details

Familial Dementia, Parkinsonism, Seizures and Spastic Paraparesis Associated with the Novel Y288H Presenilin-1 Mutation
Aging and Dementia
(-)
008
Mutations in the presenilin 1 gene (PSEN1) are the most commonly identified genetic cause Alzheimer's disease. Significant clinical heterogeneity exists within and between families having mutations of this gene.
We prospectively evaluated the proband and reviewed all available medical records and neuroimaging of other affected relatives.
Three individuals presented with young-onset spastic paraparesis, progressive cognitive impairment and parkinsonism. Two others developed young-onset cognitive impairment in their 30's, which was preceded by new-onset seizures in one. Patchy T2 signal abnormalities on magnetic resonance imaging in two individuals initially lead to erroneous diagnosis of familial multiple sclerosis. Laboratory studies in the proband demonstrated increased serum levels of A?42 and an increased A?42:A?40 ratio, supporting a role of abnormal amyloid processing in the pathogenesis of this disease. Genetic analysis identified the Y288H mutation of PSEN1.
This kindred extends the clinical and radiologic heterogeneity associated with PSEN1 mutations and suggests that PSEN1 testing should be considered in families having a strong history of ill-defined neurologic disorders when spastic paraparesis is a prominent clinical feature.
Authors/Disclosures
Meredith Wicklund, MD, FAAN (Mayo Clinic Arizona)
PRESENTER 		The institution of Dr. Wicklund has received research support from Arizona Alzheimer's Consortium. The institution of Dr. Wicklund has received research support from NIH.
Brendan J. Kelley, MD, FAAN (University of Texas Southwestern) Dr. Kelley has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Kelley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Labcorp. Dr. Kelley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Esai.
Bradley F. Boeve, MD, FAAN (Mayo Clinic) Dr. Boeve 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 Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from EIP Pharma. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care.
Orhun H. Kantarci, MD Dr. Kantarci has nothing to disclose.
John W. Day, MD, PhD (Stanford University School of Medicine) Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapy. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PepGen. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Epirium Bio. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid Biosciences. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Astellas Pharma. The institution of Dr. Day has received research support from Novartis Gene Therapy. The institution of Dr. Day has received research support from Biogen. The institution of Dr. Day has received research support from Roche/Genentech. The institution of Dr. Day has received research support from Sanofi/Genzyme. The institution of Dr. Day has received research support from Sarepta. The institution of Dr. Day has received research support from Scholar Rock. The institution of Dr. Day has received research support from AMO Pharma. The institution of Dr. Day has received research support from AnnJi. Dr. Day has received research support from CureSMA. The institution of Dr. Day has received research support from Muscular Dystrophy Association. The institution of Dr. Day has received research support from Ionis Pharmaceuticals. The institution of Dr. Day has received research support from NMD Pharma. The institution of Dr. Day has received research support from SMA Foundation. Dr. Day has received intellectual property interests from a discovery or technology relating to health care.
Mark Keegan, MD, FAAN (Mayo Clinic) Dr. Keegan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Keegan has received publishing royalties from a publication relating to health care. Dr. Keegan has received publishing royalties from a publication relating to health care.
Clifford R. Jack, Jr., MD (Mayo Clinic) The institution of Dr. Jack has received research support from NIH. The institution of Dr. Jack has received research support from Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic.
Karen Kuntz (Mayo Clinic) No disclosure on file
Matthew Baker No disclosure on file
Steven G. Younkin, MD, PhD (Mayo Clinic Jacksonville) No disclosure on file
No disclosure on file
Nilufer Taner, MD, PhD, FAAN (Mayo Clinic) The institution of Dr. Taner has received research support from NIH.
Rosa Rademakers, PhD (Mayo Clinic Dept of Neuroscience) Rosa Rademakers, PhD has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mayo Clinic. Rosa Rademakers, PhD has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arkuda Therapeutics. Rosa Rademakers, PhD has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Alzheimer Fondation. Rosa Rademakers, PhD 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 Kisick Family Foundation (FTD grant program). The institution of Rosa Rademakers, PhD has received research support from NIH. The institution of Rosa Rademakers, PhD has received research support from DOD. The institution of Rosa Rademakers, PhD has received research support from Flanders Institute for Biotechnology (VIB). The institution of Rosa Rademakers, PhD has received research support from Flanders Funds for Scientific Research.
David S. Knopman, MD, FAAN (Mayo Clinic) Dr. Knopman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DIAN TU study. The institution of Dr. Knopman has received research support from NIH.
Ronald C. Petersen, MD, PhD, FAAN (Mayo Clinic) Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co.. Dr. Petersen has received personal compensation in the range of $0-$499 for serving as a Consultant for Eisai, Inc.. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has a non-compensated relationship as a Board of Directors with American Brain Foundation that is relevant to AAN interests or activities.