Transgenic mouse brain histopathology resembles early Alzheimer's disease

Abstract

Transgenic mice expressing the 751–amino acid form of the human amyloid precursor protein develop extracellular β‐amyloid protein (Aβ)–immunoreactive deposits that increase in frequency with age. Here we show that the appearance and histological profile of deposits in the transgenic mice closely resemble those of preamyloid deposits in the brains of young adults with Down's syndrome, who presumably have the pathology of early‐stage Alzheimer's disease. Specific monoclonal antibodies reveal that material in the deposits has the free carboxyl terminus of Aβ 1‐42, and that the deposits contain material which, by immunohistochemical analysis, apparently originates from the human β‐amyloid precursor protein (βPP) transgene. In rare cases, the transgenic mouse brains contain several different histopathological characteristics of Alzheimer lesions. These features include dense Aβ immunoreactivity which co‐localizes with gliosis and with Alz50‐immunoreactive structures resembling swollen boutons of dystrophic neurites. These observations demonstrate that the murine brain is capable of reproducing several typical features of Alzheimer histopathology.