Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures

Background:The goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort.Methods:We developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF -amyloid 1-42 (A(42)) 192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio 1.5. We trained our classifier in the subcohort with CSF A(42) but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF A(42) data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia.Results:The CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%.Conclusions:Automated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future.Classification of evidence:This study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%).