Soluble derivatives of the β amyloid protein precursor in cerebrospinal fluid: Alterations in normal aging and in alzheimer’s disease

We isolated and sequenced a soluble ~25 kDa amino-terminal derivative of the (3 amyloid protein precursor (PAPP) that is readily detected in human cerebrospinal fluid (CSF). In CSF samples from 24 Alzheimer’s disease (AD) patients and 12 controls, we then quantitated this ~25 kDa form as well as the ~125 and ~105 kDa derivatives that we previously identified. Our analysis shows (1) that, in AD, there is a significant decrease in the relative amount of the ~105 kDa form and a corresponding significant increase in the relative amount of the ~25 kDa form; (2) that these changes correlate with the mental status of the AD patients; and (3) that the same changes occur to a lesser extent in elderly as compared with young control patients. These observations indicate that processing of the βAPP changes in normal individuals as they age and to a greater extent in those who develop AD. The changes in PAPP derivatives that we have observed in CSF could have major implicataions because they may reflect fundamental mechanisms responsible for amyloid deposition and can be measured in living patients.