Methods for identifying compounds effective for treating neurodegenerative disorders and for monitoring the therapeutic intervention therefor

A method of identifying compounds that modulate levels of .alpha.-sAPP or the ratio of .alpha.-sAPP to total sAPP in cerebrospinal fluid, comprising:

• administering a compound to a test subject;
• and
• detecting either:
• (i) an increase in the ratio of .alpha.-sAPP to sAPP in a sample of cerebral spinal fluid (CSF) from the subject, or
• (ii) an increase in the amount of .alpha.-sAPP in a sample of CSF from the subject, whereby effective compounds are identified,
• wherein:
• the increase is in ratio or amount compared to such ratio or amount in a sample of CSF prior to administering the compound;
• .alpha.-sAPP is a cleavage product of amyloid precursor protein (APP) that (i) reacts with an antibody specific for the N-terminus of APP, (ii) reacts with an antibody specific for an epitope in the first 17 amino acids of amyloid .beta.-protein (A.beta.), and (iii) when produced from an APP molecule, precludes formation of A.beta. from that molecule.