[The role of lipid metabolism in Alzheimer's disease].
Lipid metabolism in the central nervous system has been focused as an important factor of Alzheimer's disease, since the apolipoprotein E gene was discovered as a genetic risk for the disease. Lipid metabolism in the brain, showing relatively closed environment, necessitates lipid reutilization. Cerebrospinal fluid contains only high-density lipoproteins composed of apoE and apoJ secreted from astrocytes and of apoA-I and apoA-II transported via the blood brain barrier. These apolipoproteins can bind to beta amyloid and possibly relate to its clearance. The aggregation of phosphorylated tau, found in neurofibrillary tangles in Alzheimer's brain, is also found in the brain with Niemann-Pick disease, suggesting that the impairment of lipid transport in neuronal cells participates in Alzheimer's disease. Mitochondrial function, lipid production, and acetylcholine production are closely related, and these alterations could be involved in cholinergic dysfunction in Alzheimer's disease. The regulation of lipid metabolism in and outside the brain could be a therapeutic and preventive target for Alzheimer's disease.
Kamino
Kouzin
K
Division of Psychiatry and Behavioral Proteomics, Department of Post-Genomics and Diseases, Osaka University Graduate School of Medicine, 2-2, D3, Yamadaoka, Suita, 565-0871 Japan.
Tanaka
Toshihisa
T
Kida
Tomoyuki
T
Ohkochi
Masayasu
M
Tanii
Hisashi
H
Kudo
Takashi
T
Takeda
Masatoshi
M
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000109:Acetylcholine / Q000096:biosynthesis; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000502:physiology; D000818:Animals; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D016874:Neurofibrillary Tangles; D009473:Neuronal Plasticity; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D000105:Acetyl Coenzyme A; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000109:Acetylcholine