Accumulation of Intraneuronal Amyloid-β is Common in Normal Brain
Jeffrey A. Blair, Sandra L. Siedlak, Julie A. Wolfram, Akihiko Nunomura, Rudy J. Castellani, Sergio T. Ferreira, William L. Klein, Yang Wang, Gemma Casadesus, Mark A. Smith, George Perry, Xiongwei Zhu and Hyoung-gon Lee
Affiliation: Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA.
Keywords: Aging, Alzheimer disease, amyloid-β, amyloid-β protein precursor, immunohistochemistry, neuropathology.
Intraneuronal amyloid-β (iAβ) accumulation has been demonstrated in Alzheimer disease (AD). Although extracellular
amyloid plaques composed primarily of aggregated amyloid-β are one of the main pathological features of AD,
functional characterization of iAβ is still lacking. In this study, we identified the normal distribution of iAβ through an
analysis of hippocampal sections from a series of over 90 subjects with diverse antemortem clinical findings. In addition
to AD cases, iAβ 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 iAβ
between gender, postmortem interval, or age. While the possible pathophysiological significance of iAβ accumulation in
AD remains to be elucidated, careful examination of iAβ found in the normal brain may be informative for determining
the biological role of iAβ and how this function changes during disease. Current findings support a physiological role for
iAβ in neuronal function over the entire lifespan.
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