What is primary and what secondary for amyloid deposition in Alzheimer's disease.

The fact that physiologically beta-amyloid precursor proteins are synthesized by all cells of the body without any amyloid deposition in other organs raises a question about an isolated deposition of amyloid in the brain. One of the most important mechanisms in the pathogenesis of senile dementia of the Alzheimer type is the marked decrease of the cerebral glucose metabolism, a cholinergic deficit, by a disturbed acetyl-CoA synthesis and a critically lowered oxidative phosphorylation. Remembering that aging is the most important predisposing factor in the development of Alzheimer's disease, it is argued that a decrease of the oxidative energy metabolism in senile dementia and the resulting ATP deficit may change protein degradation, synaptic transmission and ion homeostasis.

Changes in brain glucose metabolism as a key to the pathogenesis of Alzheimer's disease.

The article discusses some aspects demonstrating that a decrease in acetylcholine synthesis in senile dementia of the Alzheimer type (SDAT) is a consequence of the strong decline in glucose turnover in the brain. This becomes obvious by the fact that acetylcoenzyme A, the key substrate of acetylcholine synthesis, is exclusively synthesized in the glycolytic pathway in the brain. This means that a single molecule of glucose synthesizes only two molecules of acetylcoenzyme A but 38 molecules of ATP.

Senile dementia: a threshold phenomenon of normal aging? A contribution to the functional reserve hypothesis of the brain.

Neurochemical investigations with normal aging brains show that in the first 70 years of life no major changes of the glycolytic pathway can be observed. Only in the following decades does a significant decrease of brain metabolic turnover occur. Changes in nerve cell size, one of the most relevant parameters in evaluating a diffuse nerve cell atrophy, appear in the brain cortex not earlier than between 85 and 94 years of age; a 21% nerve cell shrinkage is the mean.

Neurochemical enzyme changes in Alzheimer's and Pick's disease.

Neurochemical investigations of the whole temporal lobe of cases with Alzheimer's disease (n = 15); 80.7 +/- 1.7 yr), Pick's disease (n = 3; 65 +/- 1.

Glycolytic enzymes from human autoptic brain cortex: normal aged and demented cases.

The activities of glycolytic enzymes were determined in human autoptic temporal lobes from patients with different forms of dementia. For some enzymes (hexokinase, phosphofructokinase and phosphoglycerate mutase) the effect seen in dementia can be regarded as an intensification of the normal ageing affect. For other enzymes (aldolase, phosphoglucose isomerase, triosephosphate isomerase and lactate dehydrogenase) no changes in enzyme activities corresponding to those found in dementia are observed in the normal ageing process.