Pathogenesis of decreased glucose turnover and oxidative phosphorylation in ischemic and trauma-induced dementia of the Alzheimer type.
The pathogenetic mechanisms causing a dementing brain disease after temporary ischemia, heat shock, or brain trauma are surveyed. These lesions increase beta amyloid precursor protein (beta APP) synthesis. This process is potentiated by an ischemic glutamate release that opens cellular Ca2+ channels, inhibiting glucose turnover and ATP production, which is, under these conditions, accompanied by the generation of beta amyloid (beta A), even in young persons. Beta amyloid starts a vicious circle by inactivating the glycolytic key enzyme, phosphofructokinase, which, with age, exhausts the functional reserve capacity of the brain. This demonstrates that beta A is an epiphenomenon of a dementing brain disease, triggered by the disturbance of glucose turnover and oxidative phosphorylation. Clinical studies have shown that a dementing brain disease can be clearly objectified and monitored by 18F-2-deoxyglucose PET studies. This paper looks briefly at pharmacologic approaches to this disease using models of temporary ischemia, the testing of 14C-deoxyglucose turnover, or examination with 31P magnetic resonance spectroscopy techniques. In conclusion, the key process of all dementing brain diseases of the Alzheimer type is a decreased glucose turnover and subsequently decreased oxidative phosphorylation, linked directly to a secondary amyloid formation and nerve cell atrophy.
Meier-Ruge
W A
WA
Department of Pathology, University Medical School, Basel, Switzerland.
Bertoni-Freddari
C
C
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D018883:Heat Stroke / Q000150:complications / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010085:Oxidative Phosphorylation
D016564:Amyloid beta-Protein Precursor; D018698:Glutamic Acid; D005947:Glucose