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脳内脂肪酸レベルをコントロールすることがアルツハイマー病の治療に役立つ可能性がある。マウスの実験で、記憶と行動に改善が見られた。 　英国では約70万人の認知症の患者がいるが、次の世代で２倍となると予測されている。 　アルツハイマー病マウスの脳ではアラキドン酸が増加している。PLA2酵素が生成をコントロールしているため、遺伝子工学技術でマウスのPLA2レベルを下げると、記憶低下などの脳障害の進行が止まった。 　記憶に関係した海馬での増加が見られ、脳細胞を過度に刺激している可能性がある。しかし、治療に役立てるにはより多くの研究が必要である。 -------------------------------------------------- Page last updated at 23:03 GMT, Sunday, 19 October 2008 00:03 UK Fatty acids clue to Alzheimer's http://news.bbc.co.uk/2/hi/health/7676606.stm Brain Scientists want to know more about the brain changes that lead to Alzheimer's Controlling the level of a fatty acid in the brain could help treat Alzheimer's disease, an American study has suggested. Tests on mice showed that reducing excess levels of the acid lessened animals' memory problems and behavioural changes. Writing in Nature Neuroscience, the team said fatty acid levels could be controlled through diet or drugs. A UK Alzheimer's expert called the work "robust and exciting". There are currently 700,000 people living with dementia in the UK, but that number is forecast to double within a generation. Over-stimulation Scientists from Gladstone Institute of Neurological Disease and the University of California looked at fatty acids in the brains of normal mice and compared them with those in mice genetically engineered to have an Alzheimer's-like condition. They identified raised levels of a fatty acid called arachidonic acid in the brains of the Alzheimer's mice. This is cause for cautious optimism, as fatty acid levels can be controlled to some extent by diet and drugs Rebecca Wood, Alzheimer's Research Trust Its release is controlled by the PLA2 enzyme. The scientists again used genetic engineering to lower PLA2 levels in the animals, and found that even a partial reduction halted memory deterioration and other impairments. Dr Rene Sanchez-Mejia, who worked on the study, said: "The most striking change we discovered in the Alzheimer's mice was an increase in arachidonic acid and related metabolites [products] in the hippocampus, a memory centre that is affected early and severely by Alzheimer's disease." He suggested too much arachidonic acid might over-stimulate brain cells, and that lowering levels allowed them to function normally. Dr Lennart Mucke, who led the research, added: "In general, fatty acid levels can be regulated by diet or drugs. "Our results have important therapeutic implications because they suggest that inhibition of PLA2 activity might help prevent neurological impairments in Alzheimer's disease. "But a lot more work needs to be done before this novel therapeutic strategy can be tested on humans." 'Cautious optimism' Rebecca Wood, chief executive of the UK's Alzheimer's Research Trust, said: "This research on mice suggests a connection between fatty acids and the abnormal brain activity that exists in Alzheimer's disease. "This is cause for cautious optimism, as fatty acid levels can be controlled to some extent by diet and drugs. "However, it is not yet clear if these findings are applicable to humans, and a lot more research is needed before any human trials can be conducted." Professor Clive Ballard, director of Research at the Alzheimer's Society, said the work was "robust and exciting". He added: "This is a novel and potentially exciting area of research, but it is still at a very early stage. "Much more research is needed to see if fatty acids could lead to a treatment for those living with the devastating effects of Alzheimer's disease." ---------------------------------------------------- Nature Neuroscience (19 Oct 2008), doi: 10.1038/nn.2213, Article Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer’s disease Rene O Sanchez-Mejia1,2,7, John W Newman3, Sandy Toh1,4, Gui-Qiu Yu1, Yungui Zhou1, Brian Halabisky1, Moustapha Cisse´1, Kimberly Scearce-Levie1, Irene H Cheng1, Li Gan1, Jorge J Palop1, Joseph V Bonventre5 & Lennart Mucke1,4,6 Neuronal expression of familial Alzheimer’s disease–mutant human amyloid precursor protein (hAPP) and hAPP-derived amyloid-b(Ab) peptides causes synaptic dysfunction, inflammation and abnormal cerebrovascular tone in transgenic mice. Fatty acids may be involved in these processes, but their contribution to Alzheimer’s disease pathogenesis is uncertain. We used a lipidomics approach to generate a broad profile of fatty acids in brain tissues of hAPP-expressing mice and found an increase in arachidonic acid and its metabolites, suggesting increased activity of the group IV isoform of phospholipase A2 (GIVA-PLA2). The levels of activated GIVA-PLA2 in the hippocampus were increased in individuals with Alzheimer’s disease and in hAPP mice. Ab caused a dose-dependent increase in GIVA-PLA2 phosphorylation in neuronal cultures. Inhibition of GIVA-PLA2 diminished Ab-induced neurotoxicity. Genetic ablation or reduction of GIVA-PLA2 protected hAPP mice against Ab-dependent deficits in learning and memory, behavioral alterations and premature mortality. Inhibition of GIVA-PLA2 may be beneficial in the treatment and prevention of Alzheimer’s disease.

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