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Pathogenesis of Decreased Glucose Turnover and Oxidative Phosphorylation in Ischemic and Trauma‐Induced Dementia of the Alzheimer Type
Author(s) -
MEIERRUGE W. A.,
BERTONIFREDDARI C.
Publication year - 1997
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1997.tb48474.x
Subject(s) - dementia , oxidative phosphorylation , pathogenesis , medicine , amyloid (mycology) , endocrinology , ischemia , amyloid beta , glycolysis , glutamate receptor , neuroscience , disease , chemistry , pathology , biochemistry , psychology , metabolism , receptor
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 Ca 2+ 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, phos‐phofructokinase, 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 18 F‐2‐deoxyglucose PET studies. This paper looks briefly a pharmacologic approaches to this disease using models of temporary ischemia, the testing of 14 C‐deoxyglucose turnover, or examination with 31 P 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.