Accumulation of Intraneuronal Amyloid-β is Common in Normal Brain

Intraneuronal amyloid-beta (iA beta) accumulation has been demonstrated in Alzheimer disease (AD). Although extracellular amyloid plaques composed primarily of aggregated amyloid-beta are one of the main pathological features of AD, functional characterization of iA beta is still lacking. In this study, we identified the normal distribution of iA beta through an analysis of hippocampal sections from a series of over 90 subjects with diverse antemortem clinical findings. In addition to AD cases, iA beta in pyramidal neurons was readily and reproducibly demonstrated in the majority of control cases. Similar findings for controls were made across all ages, spanning from infants to the elderly. There was no correlation of iA beta between gender, postmortem interval, or age. While the possible pathophysiological significance of iA beta accumulation in AD remains to be elucidated, careful examination of iA beta found in the normal brain may be informative for determining the biological role of iA beta and how this function changes during disease. Current findings support a physiological role for iA beta in neuronal function over the entire lifespan.