%0 Journal Article
%T A¦Â34 is a BACE1-derived degradation intermediate associated with amyloid clearance and Alzheimer¡¯s disease progression
%J -
%D 2019
%R https://doi.org/10.1038/s41467-019-10152-w
%X The beta-site APP cleaving enzyme 1 (BACE1) is known primarily for its initial cleavage of the amyloid precursor protein (APP), which ultimately leads to the generation of A¦Â peptides. Here, we provide evidence that altered BACE1 levels and activity impact the degradation of A¦Â40 and A¦Â42 into a common A¦Â34 intermediate. Using human cerebrospinal fluid (CSF) samples from the Amsterdam Dementia Cohort, we show that A¦Â34 is elevated in individuals with mild cognitive impairment who later progressed to dementia. Furthermore, A¦Â34 levels correlate with the overall A¦Â clearance rates in amyloid positive individuals. Using CSF samples from the PREVENT-AD cohort (cognitively normal individuals at risk for Alzheimer¡¯s disease), we further demonstrate that the A¦Â34/A¦Â42 ratio, representing A¦Â degradation and cortical deposition, associates with pre-clinical markers of neurodegeneration. We propose that A¦Â34 represents a marker of amyloid clearance and may be helpful for the characterization of A¦Â turnover in clinical samples
%U https://www.nature.com/articles/s41467-019-10152-w