NACP, the precursor of non-A beta component of Alzheimer's disease (AD) amyloid (NAC), is a synaptic protein that could potentially be involved in AD. We studied, by dot-blot, NACP levels in the frontal cortex of AD cases staged according to severity of disease and correlated them with cognitive performance and neuropathological markers. Early AD cases showed one fold higher levels of NACP immunoreactivity (IR) compared to moderate and severe AD. Levels of NACP-IR were correlated with tangle counts (r = -0.305, P = 0.04) and Blessed score (r = -0.356, P = 0.01), but not with plaque counts (r = 0.132, P = 0.39). This study suggests that the abnormal accumulation of NACP during the early stages of AD might play an important role in the mechanisms of neurodegeneration and synaptic damage in AD.