Human apoE4-targeted replacement mice display synaptic deficits in the absence of neuropathology.

Journal Article

The human APOE*4 allele is associated with an early age of onset and increased risk of Alzheimer's disease (AD). Long before the onset of AD, cognitive deficits can be identified in APOE*4 carriers. We examined neurons in the lateral amygdala of young apolipoprotein (apo) E3 and apoE4 targeted replacement (TR) mice for changes in synaptic integrity. ApoE4 mice displayed significantly reduced excitatory synaptic transmission and dendritic arborization. Despite these changes there were no signs of gliosis, amyloid deposition or neurofibrillary tangles in these mice. To our knowledge, this is the first study to suggest that cognitive deficits in APOE*4 carriers are due to inherent defects in synaptic function that appear prior to any age-dependent markers of neuropathology.

Full Text

Duke Authors

Cited Authors

  • Wang, C; Wilson, WA; Moore, SD; Mace, BE; Maeda, N; Schmechel, DE; Sullivan, PM

Published Date

  • March 2005

Published In

Volume / Issue

  • 18 / 2

Start / End Page

  • 390 - 398

PubMed ID

  • 15686968

International Standard Serial Number (ISSN)

  • 0969-9961

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2004.10.013

Language

  • eng

Conference Location

  • United States