期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 32, 期 2, 页码 341-355出版社
IOS PRESS
DOI: 10.3233/JAD-2012-120697
关键词
Alzheimer's disease; apoE4; Arc; BDNF; beta-catenin; carbohydrates; memory impairment; mice
资金
- Sweden: Swedish Brain Power
- Sweden: Alzheimerfonden
- Sweden: Gun och Bertil Stohnes Stiftelse
- Sweden: Karolinska Institutet fund for geriatric research
- Sweden: KI Ostermans stiftelse
- Sweden: Stiftelsen Gamla Tjanarinnor
- Sweden: Stiftelsen C.M. Lerici
- Sweden: Stiftelsen Blanceflor Ludovisi-Boncompagni
- Spain: Ramon Areces foundation
- Italy: Fondazione Cassa di Risparmio di Bologna
The presence of the E4 allele of apolipoprotein E (apoE) is the strongest known genetic risk factor for sporadic Alzheimer's disease (AD). Other risk factors for developing AD have been identified, including lifestyle such as dietary habits. The present study was designed to explore the impact of the interaction between variant human apoE isoforms and a high carbohydrate diet (HCD) on mechanisms behind learning and memory retention. As an investigative model, we compared young apoE3 and apoE4 target replacement mice fed on a HCD for 6 months. Our results indicate that HCD compromises memory processes in apoE4 mice. ApoE4 mice on HCD showed decreased activity-regulated cytoskeletal-associated protein (Arc) and brain derived neurotrophic factor (BDNF) levels, as well as decreased BDNF signaling in the hippocampus. In contrast, apoE3 mice were resistant to the deleterious effects of HCD on both behavior and memory-related proteins. Our results support the hypothesis that already in mid-life, genetic, and environmental risk factors act together on the mechanisms behind cognitive impairment.
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