Metabolism-Centric Overview of the Pathogenesis of Alzheimer's Disease.
Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia. AD is characterized by the extracellular amyloid beta (Aβ) plaques and intraneuronal deposits of neurofibrillary tangles (NFTs). Recently, as aging has become a familiar phenomenon around the world, patients with AD are increasing in number. Thus, many researchers are working toward finding effective therapeutics for AD focused on Aβ hypothesis, although there has been no success yet. In this review paper, we suggest that AD is a metabolic disease and that we should focus on metabolites that are affected by metabolic alterations to find effective therapeutics for AD. Aging is associated with not only AD but also obesity and type 2 diabetes (T2DM). AD, obesity, and T2DM share demographic profiles, risk factors, and clinical and biochemical features in common. Considering AD as a kind of metabolic disease, we suggest insulin, adiponectin, and antioxidants as mechanistic links among these diseases and targets for AD therapeutics. Patients with AD show reduced insulin signal transductions in the brain, and intranasal injection of insulin has been found to have an effect on AD treatment. In addition, adiponectin is decreased in the patients with obesity and T2DM. This reduction induces metabolic dysfunction both in the body and the brain, leading to AD pathogenesis. Oxidative stress is known to be induced by Aβ and NFTs, and we suggest that oxidative stress caused by metabolic alterations in the body induce brain metabolic alterations, resulting in AD.
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.|BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Somang
S
Kang
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Yong Ho
YH
Lee
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.|BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. jelee@yuhs.
Jong Eun
JE
Lee
D052242:Adiponectin / Q000097:blood / Q000378:metabolism; D000375:Aging / Q000502:physiology / Q000523:psychology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
D052242:Adiponectin; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D015415:Biomarkers; D007328:Insulin
Alzheimer's disease; adiponectin; antioxidants; insulin; metabolic disease