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Abstract Details

Presence of Brain Amyloidosis Can Be Ascertained from Cognitive, Imaging and Peripheral Blood Protein Measures
Aging and Dementia
IN3 - (-)
004
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.
We used cognitive, imaging and proteomic data of 60 ADNI MCI participants (mean age=75.2卤8.1, mean MMSE=27.2卤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.
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.
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 Biogen. 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 $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. 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 Genentech. 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. An immediate family member of Dr. Apostolova has stock in Cassava Neurosciences. 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.
Kristy Hwang No disclosure on file
No disclosure on file
Barbara Bumstead, NP No disclosure on file
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 No disclosure on file
Paul M. Thompson, PhD (USC) No disclosure on file