Human apoE4-targeted replacement mice display synaptic deficits in the absence of neuropathology.
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.
Wang
Chunsheng
C
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Wilson
Wilkie A
WA
Moore
Scott D
SD
Mace
Brian E
BE
Maeda
Nobuyo
N
Schmechel
Donald E
DE
Sullivan
Patrick M
PM
D000342:Affective Symptoms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000679:Amygdala / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003712:Dendrites / Q000473:pathology; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D018390:Gene Targeting; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D013569:Synapses / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics*
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E