title: APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1.
abstract: The recent availability of transgenic mouse models of Alzheimer disease has allowed direct in vivo assessment of the molecular and neuropathological effects of cerebral amyloid deposition. We examined 16-month-old Tg(HuAPP695. K670N-M671L)2576 mice expressing human APP K670N-M671L (APPSw), which have amyloid deposition and behavioral deficits by 11 months of age. Transgene expression is predominantly neuronal, and results in amyloid deposits, comparable to human senile plaques, at terminal zones of transgene positive neurons in cortical and limbic regions. Amyloid deposits were associated with prominent gliosis and neuritic dystrophy, without neuronal loss in CA1, loss of synaptophysin immunoreactivity in the hippocampal dentate gyrus, or loss of messenger RNA for neuronal synaptic, cytoskeletal, or metabolic proteins. We conclude that A beta is not acutely neurotoxic, but can disrupt neuronal processes and provoke an inflammatory response.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Irizarry
authors.forename: M
authors.initials: M
authors.lastname: McNamara
authors.forename: K
authors.initials: K
authors.lastname: Fedorchak
authors.forename: K
authors.initials: K
authors.lastname: Hsiao
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D002452:Cell Count; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism*; D009415:Nerve Net / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D016708:Synaptophysin