Abstract Details

Title Presence of Brain Amyloidosis Can Be Ascertained from Cognitive, Imaging and Peripheral Blood Protein Measures

Topic Aging and Dementia

Presentation(s) IN3 - (-)

Poster/Presentation
Number 004

Objective

Background AD prevention trials will enroll cognitively normal amyloid PET-positive individuals. Amyloid PET screening is expensive. Being able to determine one's likelihood of being amyloid-positive using clinical and blood biomarkers could save time and resources.

Design/Methods We used cognitive, imaging and proteomic data of 60 ADNI MCI participants (mean age=75.2±8.1, mean MMSE=27.2±2.2). Our automated support vector machine classifier was provided age, sex, education, MMSE, Trails B, AVLT delayed recall, plasma levels of ApoE, BDNF, TNFalpha, IL13, IL6 and clusterin, hippocampal volume and ApoE genotype. Amyloid positivity was defined as mean cortical, lateral parietal and precuneal SUVR?1.6. Classifier performance was also tested in ApoE4-positive and negative subjects.

Results The non-ApoE-stratified classifiers consistently ranked ApoE genotype as the most powerful predictor of brain amyloidosis. Greatest classifier accuracy was seen for the lateral parietal (AUC=0.87) and precuneal regions (AUC=0.89). The variables selected by these classifiers included ApoE genotype, MMSE, Trails B, AVLT delayed recall, clusterin, TNF alpha and BDNF. The precuneal classifier also included IL13 and ApoE protein. In the ApoE4-stratified analyses the classifier achieved highest accuracy for parietal PIB positivity in both ApoE+ (AUC=1) and ApoE- subjects (AUC=0.9). In addition to MMSE and Trails B, CLU and BDNF were selected in the Apo4+ and AVLT, CLU and TNFalpha were selected in the ApoE4- classifier.

Conclusions Automated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with high accuracy. Such methods could have implications for clinical trial design and enrollment in the near future.

Authors/Disclosures
Liana Apostolova, MD, FAAN (Indiana University School of Medicine) PRESENTER	Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NIH. Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Apostolova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for siemens. Dr. Apostolova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Apostolova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Apostolova 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 Alzheimer Association. The institution of Dr. Apostolova has received research support from Roche Diagnostics. The institution of Dr. Apostolova has received research support from NIA. The institution of Dr. Apostolova has received research support from Alzheimer Association. The institution of Dr. Apostolova has received research support from AVID radiopharmaceuticals. The institution of Dr. Apostolova has received research support from Life Molecular Imaging. Dr. Apostolova has a non-compensated relationship as a advisor with FDA that is relevant to AAN interests or activities.
Kristy Hwang	No disclosure on file
	No disclosure on file
Barbara Bumstead, NP	Ms. Bumstead has nothing to disclose.
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.
Leslie M. Shaw, PhD (Perelman School of Med, U of PA)	Dr. Shaw has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Shaw has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Shaw has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Shaw has received research support from NIA. The institution of Dr. Shaw has received research support from MJ Fox foundation for Parkinsons Research.
John Q. Trojanowski, MD, PhD (University of PA School of Med)	Dr. Trojanowski has nothing to disclose.
Michael W. Weiner, MD	Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Dolby Family Ventures. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmaceuicals. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acumen Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Guidepoibnt. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Owkin France. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quantum Leap Health. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sai MedPartners. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MEDA Corp.. Dr. Weiner has stock in Anven. Dr. Weiner has stock in Alzeca. Dr. Weiner has stock in Alzheon, Inc.. Dr. Weiner has stock in ALZpath. The institution of Dr. Weiner has received research support from NIH/NIA; National Institutes of Health/National Institutes of Aging. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Speaker/Presenter with Merck Sharp & Dohme. Dr. Weiner has received personal compensation in the range of $0-$499 for serving as a Speaker/Presenter with BrightFocus Foundation. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Speaker/Presenter with Banner Health.
Paul M. Thompson, PhD (USC)	No disclosure on file

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