Abeta 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 protein V717F (PDAPP minigene) and develops age-related cerebral amyloid-beta protein (Abeta) deposits similar to senile plaques in Alzheimer's disease. We find age-related cortical and limbic Abeta deposition that 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 and amyloid deposition suggest that Abeta deposits occur at the terminals of overexpressing neurons. Amyloid deposition is associated with dystrophic neurites and extensive gliosis. However, stereological analysis shows that there is no overt neuronal loss in entorhinal cortex, CA1 hippocampal subfield, or cingulate cortex through 18 months of age. In addition, there is no apparent loss of mRNA encoding neuronal synaptic, cytoskeletal, or metabolic proteins. Thus, widespread Abeta deposition in 18-month-old heterozygotic mice produces neuritic alterations and gliosis without widespread neuronal death.
Irizarry
M C
MC
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Soriano
F
F
McNamara
M
M
Page
K J
KJ
Schenk
D
D
Games
D
D
Hyman
B T
BT
D000375:Aging / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D019076:Transgenes; D015854:Up-Regulation
D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger