What Is Primary and What Secondary for Amyloid Deposition in Alzheimer's Disease

Abstract

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. Therefore, a more than 50% decline of oxidative energy turnover could be a trigger for an accumulation of beta-amyloid in the brain, because the degradation of beta-amyloid precursor protein could be directly or indirectly disturbed by an ATP deficit. Amyloidosis and a cholinergic deficit in SDAT would then be a secondary phenomenon of the decreased glucose metabolism in the brain.

Minimally invasive surgical approach for three-vessel occlusion as a model of vascular dementia in the rat-brain bioenergetics assay

“…One of the most important hallmarks in the pathogenesis of senile or vascular dementia is the marked decrease of cerebral glucose metabolism [18] caused by disturbed acetyl-CoA synthesis and critically-lowered oxidative phosphorylation [19]. Our 3-VO model proved that it is very sensitive to oxidative modification of CK system (inactivation of enzymes) or oxidative phosphorylation in neuronal cells that cause cognitive impairment.…”

Causes and Consequences of Neuronal Energy Deficit in Sporadic Alzheimer's Disease

“… lactacidosis leading to a shift in the cellular redox state and pH 4 ; reduced formation of acetylcholine leading to abnormalities in muscarinergic signal transduction 7 ; reduced ATP availability leading to disturbances in protein synthesis and processing 3 …”

Mitochondrial Genome Lesions in the Pathogenesis of Sporadic Alzheimer’s Disease

“…To our knowledge, glucose turnover and oxidative phosphorylation seem to have critical function in the development of SDAT [9,21]. Therapy able to stabilize mitochondrial membranes and to amerliorate brain energy metabolism might be effective in the prevention and treatment of a dementing brain disease.…”

“…Despite the remarkable fascination of these findings, they were not able to bring us one step forward concerning the question of whether ß-amyloid accumulation constitutes the cause or a secondary phenomenon of AD [9,10].…”