Neurodegeneration in the central nervous system of apoE-deficient mice.

Published

Journal Article

Apolipoprotein E (apoE) is involved in the development and regeneration of the central nervous system (CNS). ApoE may also be necessary to maintain the integrity of the synapto-dendritic complexity. We analyzed the synaptic alterations in the CNS of apoE-deficient (knockout) mice during the aging process. In apoE-deficient homozygous mice, there was an age-dependent 15 to 40% loss of synaptophysin-immunoreactive nerve terminals and microtubule-associated protein 2-immunoreactive dendrites in the neocortex and hippocampus, when compared to controls. Dendritic alterations were observed as early as 4 months of age. Ultrastructural analysis revealed extensive dendritic vacuolization and disruption of the endomembrane system and cytoskeleton in apoE-deficient homozygous mice. Further immunocytochemical studies of the neuronal cytoskeleton showed that in apoE-deficient mice there was a decrease in the immunoreactivity of alpha and beta tubulin (but not kinesin) in the cell bodies and processes. These results support the contention that apoE might play an important role in maintaining the stability of the synapto-dendritic apparatus and that altered or deficient functioning of this molecule could underlie the synaptic and cytoskeletal alterations in Alzheimer's disease.

Full Text

Cited Authors

  • Masliah, E; Mallory, M; Ge, N; Alford, M; Veinbergs, I; Roses, AD

Published Date

  • December 1995

Published In

Volume / Issue

  • 136 / 2

Start / End Page

  • 107 - 122

PubMed ID

  • 7498401

Pubmed Central ID

  • 7498401

Electronic International Standard Serial Number (EISSN)

  • 1090-2430

International Standard Serial Number (ISSN)

  • 0014-4886

Digital Object Identifier (DOI)

  • 10.1006/exnr.1995.1088

Language

  • eng