Cerebrospinal fluid Abeta40 and Abeta42: natural course and clinical usefulness.

Amyloid beta protein 40 (Abeta40) and 42 Abeta42, major components of senile plaque amyloids, are physiological peptides present in the brain, cerebrospinal fluid (CSF) and plasma. The levels of CSF Abeta40 and Abeta42(43) show a U-shaped natural course in normal aging. The increase of Abeta42(43) over 60 years of age is inhibited in Alzheimer's disease (AD). This specific alteration of CSF Abeta42(43) correlates with Abeta deposits in the AD brain providing a biological basis for a biomarker of AD. In the GTT2 study, assays of the CSF Abeta ratio ((Abeta40/ Abeta42(43)) showed a diagnostic sensitivity (59%) and specificity (88%) compared with non-AD type dementia and controls. The levels of the Abeta ratio increased from early to late stages of AD. Combination assays of CSF tau and Abeta ratio provided further efficient diagnostic sensitivity (81%) and specificity (87%). The reliability of the assay may prompt worldwide usage of these CSF biomarkers for Alzheimer's patients.