Analysis of APL1beta28, a surrogate marker for Alzheimer Abeta42, indicates altered precision of gamma-cleavage in the brains of Alzheimer disease patients.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Currently, therapeutic intervention after the disease onset is difficult because progressive neuronal death precedes clinical symptoms. Available medicines for AD, such as AchE inhibitors, transiently slow the progression of the dementia symptoms, but they do not inhibit the pathological process. At present, next generation anti-AD drugs are in development in many pharmaceutical companies. Importantly, most of them are to inhibit the progress of the pathological process and, thus, at the same time, the establishment of a highly probable prediction of future AD onset is inseparable. AD is now diagnosed using clinical criteria coupled with brain imaging systems such as SPECT and PET. To diagnose AD cases before the appearance of clinical symptoms, it will be necessary to (a) establish new, more sensitive clinical criteria, (b) develop methods for detecting the pathological accumulation of proteins (e.g. Abeta) in the brain, or (c) develop biomarkers for predicting the accumulation of Abeta/tau in the brain. Our recent discovery of APL1beta28, a possible biomarker of AD, may help in the development of early detection methods for AD. Copyright 2010 S. Karger AG, Basel.