Biomarkers for Alzheimer's Disease

There is consistent evidence that levels of 42 amino acid Aß (Aß42) and tau/p181tau in CSF correlate with late-onset AD status and may be useful biomarkers and endophenotypes for late-onset AD. Recent work shows that CSF Aß42 levels vary inversely with Aß deposition as detected in vivo with the positron emission tomography imaging agent Pittsburgh compound B. CSF Aß42 and tau/p181tau levels predict future cognitive decline in longitudinal studies. Furthermore, elevated 40 amino acid Aß (Aß40) levels in a transgenic model of Aß deposition substantially delayed Aß42 deposition in these animals. These data show that CSF Aß levels and tau/p181tau levels are correlated with late-onset AD status, severity and pathological features, confirming their utility as endophenotypes for genetic studies of late-onset AD. The use of CSF protein levels as endophenotypes is a novel innovative approach to understanding late-onset AD genetics.