TRANSGENIC MOUSE-BRAIN HISTOPATHOLOGY RESEMBLES EARLY ALZHEIMERS-DISEASE

Transgenic mice expressing the 751-amino acid form of the human amyloi d precursor protein develop extracellular beta-amyloid protein (A beta )-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 b rains of young adults with Down's syndrome, who presumably have the pa thology of early-stage Alzheimer's disease. Specific monoclonal antibo dies reveal that material in the deposits has the free carboxyl termin us of A beta 1-42, and that the deposits contain material which, by im munohistochemical analysis, apparently originates from the human beta- amyloid precursor protein (beta PP) transgene. In rare cases, the tran sgenic mouse brains contain several different histopathological charac teristics of alzheimer lesions. These features include dense A beta im munoreactivity which co-localizes with gliosis and with Alz50-immunore active structures resembling swollen boutons of dystrophic neurites. T hese observations demonstrate that the murine brain is capable of repr oducing several typical features of Alzheimer histopathology.`