アルツハイマー病とホモシステイン(<特集>ビタミンB研究委員会平成24年度シンポジウム「B群ビタミンによる疾患の治療」)

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Recently, with the increase of aged people in Japan, the number of people with dementia has been markedly increasing. It was estimated that the number of people with dementia is 4.62 million people in Japan. The most important causes of dementia are Alzheimer's disease (AD), dementia with lewy bodies (DLB), vascular dementia (VD), and frontotemporal dementia (FTD). As treatable dementia, vitamin deficiencies, including vitamin B_1 and B_<12>, and folate deficiencies are important causes. Vitamin B_<12> and folate work as a cofactor of the conversion of homocysteine (Hcy) to methionine. Thus, vitamin B_<12> and folate deficiencies can be the causes of hyperhomocysteinemia. It was reported that hyperhomocysteinemia is an independent risk factor of dementia, including AD (Seshadri et al., 2012). The pathological hallmarks of AD are neurofibrillary tangles (NFT) and senile plaques. The main component of NFT is highly phosphorylated tau protein. We have examined the effect of Hcy on tau metabolism using an inducible model of tauopathy (M1C cells), which express wild type tau protein (4R0N) via tetracycline Off (Tet-Off) induction and neuronal culture (Hamano et al., Neurobiol Aging 2012). Western blot analysis revealed that the administration of L-Hcy increased total tau and phosphorylated tau protein levels. An increase in tau species with C-terminal truncation by caspase 3 was also noted. Activation of caspase 3 was also observed. In a clinical study, folate and vitamin B_<12> levels, as well as Hcy levels, were examined in all patients of the dementia outpatient clinic of University of Fukui. The patients with folate or vitamin B12 deficiency showed hyperhomocysteinemia. After folate supplementation, plasma Hcy levels returned to normal levels. Cognitive functions also improved. Vitamin B_<12> or folate supplementation therapy may prevent the progression of AD pathology in the brain via Hcy reduction.
日本ビタミン学会の論文
2014-02-25

アルツハイマー病とホモシステイン(<特集>ビタミンB研究委員会平成24年度シンポジウム「B群ビタミンによる疾患の治療」)

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アルツハイマー病とホモシステイン(<特集>ビタミンB研究委員会 平成24年度シンポジウム「B群ビタミンによる疾患の治療」)

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アルツハイマー病とホモシステイン(<特集>ビタミンB研究委員会平成24年度シンポジウム「B群ビタミンによる疾患の治療」)