ApoE4 in mice induces age-dependent brain hypoperfusion, neuronal, glial and microvascular damage, and cognitive impairment, which can be prevented by feeding acetyl-L-carnitine and R-lipoic acid

被引：0

作者：

Aliev, G. ^{[1
]}

Liu, J. ^{[2
]}

Xu, K. ^{[3
]}

Puchowicz, M. ^{[3
]}

Siedlak, S. L. ^{[4
]}

Shenk, J. C. ^{[1
]}

Smith, M. A. ^{[4
]}

Gasimov, E. ^{[1
]}

Obrenovich, M. E. ^{[4
]}

Fischbach, K. ^{[1
]}

Koistinaho, J. ^{[5
]}

LaManna, J. C. ^{[3
]}

Ames, B. N.

Perry, G. ^{[1
,4
]}

机构：

[1] Univ Texas San Antonio, Dept Biol, Coll Sci, 1 UTSA Circle, San Antonio, TX 78249 USA

[2] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA

[3] Case Western Reserve Univ, Sch Med, Dept Anat, Cleveland, OH 44106 USA

[4] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA

[5] Univ Kuopio, AI Virtanen Inst Mol Sci, Kuopio 70210, Finland

来源：

NEW TRENDS IN ALZHEIMER AND PARKINSON RELATED DISORDERS: ADPD 2007 | 2007年

关键词：

ApoE4; Alzheimer's disease; cerebral blood flow; electron microscopy; vascular and mitochondrial damage; mitochondrial antioxidant and cognitive performance;

D O I：

暂无

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Transgenic mice carrying the E4 allele of apolipoprotein E gene related to Alzheimer's disease (AD) seem an excellent animal model for studying preclinical treatments of ApoE-related cognitive deficits because the animals express human ApoE4 at human levels in glia and exhibit measurable cognitive impairments. We investigated the role of age-dependent ApoE4 effects on cerebral blood flow (CBF) as an initiator of brain hypoperfusion using ApoE4 transgenic mice compared to age-matched wild-type (WT) mice using [C-14] iodoantipyrene autoradiography. ApoE4 associated factors reduces. CBF gradually to create brain hypoperfusion when compared to WT and the differences in CBF are greatest as animals age from 6-weeks to 12-months. Transmission electron microscopy and immunodecoration with colloidal gold immunocytochemistry showed that structural damage in young and aged microvessel endothelium of ApoE4 animals extended to the matrix of perivascular cells, perivascular nerve terminals and to hippocampal neurons and glial cells. Moreover, these abnormalities coexist with the mitochondrial structural alteration and mitochondrial DNA (mtDNA) overproliferation and/or deletion in all brain cellular compartments. Spatial memory and temporal memory tests showed a trend in improving cognitive function in ApoE4 mice fed acetyl-L-carnitine and R-lipoic acid (ALCAR+LA). Our findings indicate for the first time that the ApoE4 genotype induces mitochondrial changes and associated structural damage that may explain the age-dependent pathology seen in AD and potentially new and more effective treatment strategies in the near future.

引用

页码：105 / +

页数：8