Abstract Details

Title Progressive Amnestic Dementia, Hippocampal Sclerosis, and Mutation in C9orf72

Topic Aging and Dementia

Presentation(s) P05 - (-)

Poster/Presentation
Number 099

Objective

Background BACKGROUND: The most common cause of familial frontotemporal lobar degeneration with TAR DNA-binding protein-43 (FTLD-TDP) has recently been found to be an expansion of a hexanucleotide repeat (GGGGCC) in a noncoding region of the gene C9ORF72. Hippocampal sclerosis (HpScl) is a common finding in FTLD-TDP.

Design/Methods DESIGN/METHODS: We identified a single HpScl autopsy case with a repeat expansion in C9ORF72. Mutation screening was performed with repeat-primed polymerase chain reaction and confirmed with southern blotting.

Results RESULTS: The patient had a 14-year history of a slowly progressive amnestic syndrome and a clinical diagnosis of probable Alzheimer's disease. Neuropsychological testing revealed memory impairment, but no deficits in other cognitive domains. Autopsy showed hippocampal sclerosis with TDP-43 immunoreactive neuronal inclusions relatively limited to limbic lobe structures. Neuritic pathology immunoreactive for p62 was more frequent than TDP-43 in amygdala and hippocampus. Frequent p62 positive neuronal inclusions were present in cerebellar granule neurons as is typical of C9ORF72 mutation carriers. There was no significant frontotemporal lobar degeneration or motor neuron disease.

Conclusions CONCLUSIONS: The findings in this patient suggest that the clinical and pathological spectrum of C9ORF72 repeat expansion is wider than frontotemporal dementia and motor neuron disease, including cases of progressive amnestic dementia with restricted TDP-43 pathology.

Authors/Disclosures
Dennis W. Dickson, MD (Mayo Clinic) PRESENTER	Dr. Dickson has nothing to disclose.
Melissa Murray, PhD (Mayo Clinic)	Dr. Murray has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Avid Radiopharmaceuticals. The institution of Dr. Murray has received research support from National Institute on Aging. The institution of Dr. Murray has received research support from Alzheimer's Association. The institution of Dr. Murray has received research support from Chan Zuckerberg Initiative.
Ira J. Goodman, MD (The Compass Clinic)	No disclosure on file
Brian G. Weinshenker, MD, FAAN (University of Virginia Health System)	Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CANbridge Pharmaceuticals. Dr. Weinshenker has received personal compensation in the range of $0-$499 for serving as a Consultant for CALIBR. Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Group (Chugai, Genentech, Roche). Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharmaceuticals. Dr. Weinshenker has received research support from Guthy Jackson Charitable Foundation. Dr. Weinshenker has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Naomi Kouri	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
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.

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