Apolipoprotein E4 domain interaction: Synaptic and cognitive deficits in mice
نویسندگان
چکیده
منابع مشابه
Androgens protect against apolipoprotein E4-induced cognitive deficits.
Compared with apolipoprotein (apo) E2 and E3, apoE4 increases the risk of Alzheimer's disease (AD), but it remains unknown how apoE4 affects neuronal function. ApoE4 interacts with female gender, further increasing the risk of AD and decreasing treatment response. Female mice are also more susceptible to apoE4-induced impairments of spatial learning and memory than male mice. To assess the role...
متن کاملApolipoprotein E4 domain interaction accelerates diet-induced atherosclerosis in hypomorphic Arg-61 apoe mice.
OBJECTIVE Apolipoprotein (apo) E4 is an established risk factor for atherosclerosis, but the structural components underlying this association remain unclear. ApoE4 is characterized by 2 biophysical properties: domain interaction and molten globule state. Substituting Arg-61 for Thr-61 in mouse apoE introduces domain interaction without molten globule state, allowing us to delineate potential p...
متن کاملActivation of the amyloid cascade in apolipoprotein E4 transgenic mice induces lysosomal activation and neurodegeneration resulting in marked cognitive deficits.
The allele E4 of apolipoprotein E (apoE4), the most prevalent genetic risk factor for Alzheimer's disease, is associated histopathologically with elevated levels of brain amyloid. This led to the suggestion that the pathological effects of apoE4 are mediated by cross-talk interactions with amyloid beta peptide (Abeta), which accentuate the pathological effects of the amyloid cascade. The mechan...
متن کاملCarboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice.
Apolipoprotein (apo) E4 increases the risk and accelerates the onset of Alzheimer's disease (AD). However, the underlying mechanisms remain to be determined. We previously found that apoE undergoes proteolytic cleavage in AD brains and in cultured neuronal cells, resulting in the accumulation of carboxyl-terminal-truncated fragments of apoE that are neurotoxic. Here we show that this fragmentat...
متن کاملIntroduction of human apolipoprotein E4 "domain interaction" into mouse apolipoprotein E.
Human apolipoprotein E4 (apoE4) binds preferentially to lower density lipoproteins, including very low density lipoproteins, and is associated with increased risk of atherosclerosis and neurodegenerative disorders, including Alzheimer's disease. This binding preference is the result of the presence of Arg-112, which causes Arg-61 in the amino-terminal domain to interact with Glu-255 in the carb...
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ژورنال
عنوان ژورنال: Alzheimer's & Dementia
سال: 2008
ISSN: 1552-5260
DOI: 10.1016/j.jalz.2008.01.006