Low Normal Cerebrospinal Fluid A-beta-42 Levels Predict Clinical Progression in Nondemented Subjects

We studied whether continuous lower normal cerebrospinal fluid (CSF) amyloid beta 1-42 (>= 640pg/ml) levels were related with rate of clinical progression in a sample of 393 nondemented memory clinic patients. Lower normal levels were associated with faster clinical progression, and this depended on baseline cognitive status (subjective cognitive decline: hazard ratio [HR] = 0.57, p <0.05; mild cognitive impairment: HR = 0.19, p <.01), indicating that normal CSF amyloid levels do not exclude incident Alzheimer disease. These findings suggest that research on preclinical markers for Alzheimer disease should take the continuum of CSF amyloid beta 1-42 levels within the normal range into account.