Cerebrometabolic abnormalities in Alzheimer's disease.
Extensive, replicated evidence in patients in vivo and in Alzheimer (AD) tissues in vitro indicates that impaired brain metabolism is one of the cardinal and essentially invariable events in AD. The degree of impairment in brain metabolism is proportional to the degree of clinical disability, both in vivo and in vitro. The 'cerebrometabolic lesion' cannot be attributed to 'slower thinking' or 'brain atrophy', because of quantitative considerations and because the metabolic lesion precedes the development of neuropsychological abnormalities or decreases in brain mass detectable by modern imaging techniques. The causes of the cerebrometabolic lesion in AD are not well defined. Free radicals seem likely to be involved, including free radicals generated from Alzheimer amyloid. Thus, the importance of the cerebrometabolic lesion is entirely compatible with most versions of the widely accepted 'amyloid cascade hypothesis' of AD. A variety of plausible, redundantly documented mechanisms are compatible with the proposal that the cerebrometabolic lesion is a proximate cause of the clinical disability in AD. In agreement with these findings, recent attempts to treat the cerebrometabolic lesion in AD have given encouraging preliminary results. The cerebrometabolic lesion in AD deserves further study.
D000544:Alzheimer Disease / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001928:Brain Diseases, Metabolic / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology
D016229:Amyloid beta-Peptides; D005609:Free Radicals