Time Course of the Development of Alzheimer-Like Pathology in the Doubly Transgenic PS1+APP Mouse

Details

• Personal Author:
  Boyett KW ; Connor K ; DiCarlo G ; Gordon MN ; Holcomb LA ; Jantzen PT ; Melachrino J ; Morgan D ; O'Callaghan JP ; Wilcock D
• Description:
  Doubly transgenic mice expressing both a mutated amyloid precursor protein and a mutated presenilin-1 protein accumulate A(beta) deposits as they age. The early A(beta) deposits were found to be primarily composed of fibrillar A(beta) and resembled compact amyloid plaques. As the mice aged, nonfibrillar A(beta) deposits increased in number and spread to regions not typically associated with amyloid plaques in Alzheimer's disease. The fibrillar, amyloid-containing deposits remained restricted to cortical and hippocampal structures and did not increase substantially beyond the 12-month time point. Even at early time points, the fibrillar deposits were associated with dystrophic neurites and activated astrocytes expressing elevated levels of glial fibrillary acidic protein. Microglia similarly demonstrated increased staining for complement receptor-3 in the vicinity of A(beta) deposits at early time points. However, when MHC-II staining was used to assess the degree of microglial activation, full activation was not detected until mice were 12 months or older. Overall, the regional pattern of A(beta) staining resembles that found in Alzheimer disease; however, a progression from diffuse A(beta) to more compact amyloid deposits is not observed in the mouse model. It is noted that the activation of microglia at 12 months is coincident with the apparent stabilization of fibrillar A(beta) deposits, raising the possibility that activated microglia might clear fibrillar A(beta) deposits at a rate similar to their rate of formation, thereby establishing a relatively steady-state level of amyloid-containing deposits. [Description provided by NIOSH]
• Subjects:
  Age Factors Animals Energy Metabolism Laboratories Nervous System Nervous System Diseases Occupational Health Pathology Safety
• Keywords:
  Age-factors Animal-studies Brain-disorders Laboratory-animals Metabolism Mutation Neurological-reactions Neurons Peptides Pharmacology Proteins Therapeutic-agents

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• ISSN:
  0014-4886
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Florida ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  183-195
• Volume:
  173
• Issue:
  2
• NIOSHTIC Number:
  nn:20023373
• Citation:
  Exp Neurol 2002 Feb; 173(2):183-195
• Contact Point Address:
  Alzheimer Research Laboratory, Department of Pharmacology, University of South Florida, Tampa, Florida 33612-4799, USA
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  True
• Source Full Name:
  Experimental Neurology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8e7c724e88b5bde0d505a2e43063e7e0d8eb9da0ffed07e7fd471e5674956cb40f82098b1f48047596096b20600a54bcb9e734b04365723e041ba7d21802659d
• Download URL:
  https://stacks.cdc.gov/view/cdc/195844/cdc_195844_DS1.pdf
• File Type:
  [PDF - 901.20 KB ]