A-BETA DEPOSITION IS ASSOCIATED WITH NEUROPIL CHANGES, BUT NOT WITH OVERT NEURONAL LOSS IN THE HUMAN AMYLOID PRECURSOR PROTEIN V717F (PDAPP) TRANSGENIC MOUSE

The PDAPP transgenic mouse overexpresses human amyloid precursor prote in V717F (PDAPP minigene) and develops age-related cerebral amyloid-be ta protein (A beta) deposits similar to senile plaques in Alzheimer's disease. We find age-related cortical and limbic A beta deposition tha t begins at 8 months and progresses to cover 20-50% of the neuropil in cingulate cortex, entorhinal cortex, and hippocampus of 18-month-old heterozygotic animals. The regional patterns of transgene expression a nd amyloid deposition suggest that A beta deposits occur at the termin als of overexpressing neurons. Amyloid deposition is associated with d ystrophic neurites and extensive gliosis. However, stereological analy sis shows that there is no overt neuronal loss in entorhinal cortex, C AI hippocampal subfield, or cingulate cortex through 18 months of age. In addition, there is no apparent loss of mRNA encoding neuronal syna ptic, cytoskeletal, or metabolic proteins. Thus, widespread AP deposit ion in 18-month-old heterozygotic mice produces neuritic alterations a nd gliosis without widespread neuronal death.