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. 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.
Meier-Ruge
W
W
Department of Pathology, University Medical School Basel, Switzerland.
Iwangoff
P
P
Bertoni-Freddari
C
C
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000686:Amyloidosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D010766:Phosphorylation
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor