P3-265: development of an indicator cell assay for blood-based diagnosis of alzheimer's disease

We are developing an indicator cell assay platform (iCAP) for blood-based diagnosis of early stages of Alzheimer's disease (AD). This assay uses standardized, commercially-sourced neurons from a single normal individual as biosensors that detect and respond to AD signals in plasma. The diagnostic readout is the expression level of a small number of selected genes in the indicator cells. We developed an iCAP for AD diagnosis and trained and validated iCAP classifiers with plasma samples from three separate sources. Case samples were from subjects with presymptomatic AD or mild cognitive impairment (MCI) due to AD, and control samples were from cognitively normal individuals or patients with non-AD dementia. Classes were defined by CDR scores and Abeta42 levels detected by imaging or CSF analysis. Classifiers were tested by blind independent validation at two stages of data collection. With training and validation sets of 101 and 41 samples, respectively, the assay achieved 69% sensitivity and 91% specificity in distinguishing early stages of AD from normal controls (AUC of ROC = 0.76; ANOVA p-value 0.0065). With training and validation sets of 186 and 50, respectively, the assay distinguished subjects at early stages of AD from normal controls and those with non-AD dementia with AUC of ROC = 0.68 (p-value 0.023; FDR 0.14). Both classifiers used samples from 3 separate sources. This work establishes a paradigm for using cultured cells as biosensors for blood-based diagnosis of AD before clinical onset.