Title:Association of Amyloid Burden, Brain Atrophy and Memory Deficits in Aged Apolipoprotein ε4 Mice
VOLUME: 11 ISSUE: 3
Author(s):Junxiang Yin, Gregory H. Turner, Stephen W. Coons, Marwan Maalouf, Eric M. Reiman and Jiong Shi
Affiliation:Department of Neurology, Barrow Neurological Institute, St. Joseph Hospital and Medical Center, 500 W Thomas Road, Suite 300, Phoenix AZ 85013, USA.
Keywords:Alzheimer’s disease (AD), apolipoprotein E ε4 allele (ApoE4), beta amyloid (Aβ), hippocampus, memory, 7 tesla
(T) magnetic resonance imaging (7T-MRI).
Abstract:Apolipoprotein E ε4 allele (ApoE4) has been associated with increased risk of sporadic Alzheimer’s disease
(AD) and of conversion from mild cognitive impairment to AD. But the underlying mechanism of ApoE4 affecting brain
atrophy and cognition is not fully understood. We investigated the effect of ApoE4 on amyloid beta (Aβ) protein burden
and its correlation with the structure change of hippocampus and cortex, cognitive and behavioral changes in ApoE4
transgenic mice. Male ApoE4 transgenic mice and age-matched control mice at age 12 months and 24 months were tested
in the Morris Water Maze (MWM). Brain volume changes (including whole brain, hippocampus, cortex, total ventricles
and caudate putamen) were assessed by using small animal 7T-MRI. Aβ level was assessed by immunohistochemistry
(IHC) and immunoprecipitation/western blot. In MWM, escape latency was longer and time spent in the target quadrant
was shorter in aged ApoE4 mice (12- and 24-month-old), suggesting age- and ApoE4-dependent visuospatial deficits. Atrophy
on MRI was prominent in the hippocampus (p=0.039) and cortex (p=0.013) of ApoE4 mice (24-month-old) as
compared to age-matched control mice. IHC revealed elevated Aβ deposition in the hippocampus. Consistently, both
soluble and insoluble Aβ aggregates were increased in aged ApoE4 mice. This increase was correlated inversely with hippocampal
atrophy and cognitive deficits. These data give further evidence that ApoE4 plays an important role in brain atrophy
and memory impairment by modulating amyloid production and deposition.
