Effects of Alzheimer's amyloid-beta and tau protein on mitochondrial function -- role of glucose metabolism and insulin signalling.
Alzheimer's disease (AD) is the most frequent form of dementia among the elderly and is characterized by neuropathological hallmarks of extracellular amyloid-beta (Abeta) plaques and intracellular neurofibrillary tangles composed of abnormally hyperphosphorylated microtubular protein tau in the brains of AD patients. Of note, current data illustrate a complex interplay between the amyloid and tau pathology during the course of the disease. We hypothesize a direct impact of abnormally phosphorylated tau and Abeta on proteins/enzymes involved in metabolism, respiratory chain function and cellular detoxification. Probably at the level of mitochondria, both Alzheimer proteins exhibit synergistic effects finally leading to/accelerating neurodegenerative mechanisms. Moreover, accumulating evidence that mitochondria failure, reduced glucose utilization and deficient energy metabolism occur already very early in the course of the disease suggests a role of impaired insulin signalling in the pathogenesis of AD. Thus, this review addresses also the question if mitochondrial dysfunction may represent a link between diabetes and AD.
Rhein
Virginie
V
Neurobiology Laboratory, Psychiatric University Clinics Basel, Basel, Switzerland. virginie.rhein@upkbs.ch
Eckert
Anne
A
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D015398:Signal Transduction; D013002:Somatomedins / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D007328:Insulin; D013002:Somatomedins; D016875:tau Proteins