Toward a Reliable Distinction Between Patients with Mild Cognitive Impairment and Alzheimer-Type Dementia Versus Major Depression

Background Cerebrospinal fluid (CSF) levels of soluble amyloid precursor protein (sAPP) and its α-secreted form (α-sAPP) were investigated as a means to distinguish between individuals with mild cognitive impairment (MCI) and Alzheimer-type dementia (DAT) and those with major depressive episode (MDE) showing secondary memory deficits. Methods Twenty-seven patients with MCI, 32 with probable DAT, and 24 with MDE attending a memory clinic were studied. Cerebrospinal fluid levels of sAPP/amyloid precursor-like protein 2 (APLP2) and α-sAPP were detected by Western blotting. Results Patients with MDE had the highest CSF levels of total sAPP/APLP2 as compared with MCI and DAT patients (p< .001); sAPP/APLP2 levels were higher in MCI than in DAT subjects. Whereas α-sAPP levels did not differ between the MCI and DAT groups, median levels of this peptide were significantly lower in MCI and DAT versus MDE patients. Conclusions Soluble amyloid precursor protein/APLP2 and α-sAPP concentrations in CSF can differentiate between DAT and MCI versus MDE, facilitating early ameliorative interventions and appropriate treatment regimens.