TY - JOUR T1 - C99, not beta-amyloid, is associated with selective death of vulnerable neurons in Alzheimer's disease. JF - bioRxiv DO - 10.1101/527572 SP - 527572 AU - Maria Pulina AU - Maya Hopkins AU - Vahram Haroutunian AU - Paul Greengard AU - Victor Bustos Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/22/527572.abstract N2 - Amyloid Precursor Protein (APP) and its cleavage product beta-amyloid are widely believed to be key players in the development of Alzheimer's disease (AD). However, the distribution of amyloid deposits in the brain does not correlate well with disease progression. Therefore, it seemed possible that APP metabolites other than beta-amyloid might make a strong contribution to AD pathology. We developed a sensitive assay adapted to the detection of C99, an intermediate in the conversion of APP to beta-amyloid. Brain tissue sections were obtained from patients suffering from sporadic AD and non-demented controls. Our results demonstrate that C99 levels, but not Abeta levels, correlate with the degree of vulnerability to neurodegeneration and cognitive impairment in patients suffering from AD. ER -