C99 selectively accumulates in vulnerable neurons in Alzheimer’s disease

Abstract

IntroductionThe levels and distribution of amyloid deposits in the brain does not correlate well with Alzheimers disease (AD) progression. Therefore, it is likely that Amyloid-precursor-protein proteolytic fragments other than beta-amyloid contribute to the onset of AD.\n\nMethodsWe developed a sensitive assay adapted to the detection of C99, the direct precursor of beta-amyloid. Three postmortem groups were studied: control with normal and stable cognition; subjects with moderate AD, and individuals with severe AD. The amount of C99 and beta-amyloid was quantified and correlated with the severity of AD.\n\nResultsC99 accumulates in vulnerable neurons, and its levels correlate with the degree of cognitive impairment in patients suffering from AD. In contrast, beta-amyloid levels are increased in both vulnerable and resistant brain areas.\n\nDiscussionThese results raise the possibility that C99, rather than beta-amyloid plaques, is responsible for the death of nerve cells in Alzheimers disease.