Abstract Details

Title A negative florbetaben PET scan reliably excludes amyloid pathology as confirmed by histopathology in a large Phase 3 trial

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) (-)

Poster/Presentation
Number 004

Objective

Background The phase 3 study of florbetaben is the largest study to date, which demonstrates a strong correlation of tracer uptake and amyloid pathology.

Design/Methods Three independent readers visually assessed florbetaben PET scans from 74 end-of-life subjects (clinical diagnosis: 57 AD; 3 DLB; 8 non-demented volunteers; 6 other dementia) who underwent brain autopsy and final neuropathological diagnosis. The scan assessment was compared with the presence/absence of neuritic beta-amyloid plaques determined according to CERAD criteria.

Results Presence of beta-amyloid was confirmed by histopathology in 47 cases: 44/57 AD subjects, 1/3 DLB patient, 1/6 other dementia subject and 1/8 non-demented volunteer. Florbetaben scans were correctly read as positive in 46 of these 47 cases. No Aß-plaques were found in 27 subjects, of these n=4 had no neurodegenerative pathologies and were correctly read PET-negative; and n=23 had other non-AD neurodegenerative pathologies like Parkinson’s-disease, hippocampal sclerosis dementia, frontotemporal lobar dementia or multi-system neuronal and glial tauopathy or Pick’s disease; 20 of these 23 scans were correctly read PET-negative.The resulting sensitivity and specificity of the majority read was 97.9% and 88.9%, respectively. The negative predictive value of florbetaben was 96%.

Conclusions Florbetaben imaging can reliably exclude amyloid pathology as demonstrated by the high negative predictive value. It is a valuable adjunct for the exclusion of Alzheimer’s disease or differential diagnosis of dementia. A negative scan should encourage the physician to search for other causes of cognitive decline and tailor available treatment options.

Authors/Disclosures
Marwan N. Sabbagh, MD, FAAN (Barrow Neurological Institute)	Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genetech=Roche. Dr. Sabbagh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novo Nordisk. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Synaptogenix. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant Health. Dr. Sabbagh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Anavex. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cognito Therapeutics. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Sabbagh 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 CervoMed. Dr. Sabbagh has stock in Neurotau. Dr. Sabbagh has stock in Seq Biomarque. Dr. Sabbagh has stock in uMethod Health. Dr. Sabbagh has stock in Athira. Dr. Sabbagh has stock in Lighthouse Pharmaceuticals. Dr. Sabbagh has stock in Alzheon. The institution of Dr. Sabbagh has received research support from NIH. The institution of Dr. Sabbagh has received research support from ADDF.
John P. Seibyl, MD	Dr. Seibyl has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Invicro. Dr. Seibyl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Seibyl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Life Molecular Imaging. Dr. Seibyl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Seibyl has received stock or an ownership interest from Invicro.
Andrew Stephens, MD, PhD	No disclosure on file
	No disclosure on file
Kenji Ishii, MD (Tokyo Metropolitan Institute for Geriatrics and Gerontology)	No disclosure on file
Masaki Takao, MD, PhD (Department of Laboratory Medicine, National Center of Neurology and Psychiatry)	No disclosure on file
	No disclosure on file
Shigeo Murayama, MD, PhD (Brain Bank for Aging Research (Neuropathology), TMIGG)	No disclosure on file
Christopher Rowe, MD (Austin and Repatriation Medical Centre)	Dr. Rowe has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Rowe has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Rowe has received research support from Cerveau Technologies. The institution of Dr. Rowe has received research support from Eisai. The institution of Dr. Rowe has received research support from Biogen.
	No disclosure on file
	No disclosure on file
Helen Tremlett, PhD, BPharm (University of British Columbia)	Dr. Tremlett has nothing to disclose.
Osama Sabri, MD, PhD (Dept. of Nuclear Medicine, University of Leip)	No disclosure on file

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