Stress-adaptation failure hypothesis of Alzheimer's disease.
It is proposed that the higher incidence of chronic stress-adaptation failure in patients with Alzheimer's disease is of specific etiopathological significance. Such chronic stress-adaptation failure leads to a vicious circular reaction, namely: intense, stressful stimuli----neocortico-limbic excitation----hypothalamo-pituitary-adrenocortical (HPA) axis activation----excessive secretion of neurohormones including cortisol----stimulation of inhibitory glucocorticoid sensitive hippocampal neurons----failure to terminate the HPA axis response----chronic excessive secretion of neurohormones including cortisol----overstimulation degeneration of glucocorticoid sensitive hippocampal inhibitory neurons----progressive cognitive-affective behavioral disorganizational failure which is typical of dementia of the Alzheimer's type. Possibilities of neuropharmacological corrections and neurobehavioral re-education are suggested.
Deshmukh
V D
VD
Department of Neurology, University of Florida, Jacksonville 32209.
Deshmukh
S V
SV
D000222:Adaptation, Physiological; D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology; D015415:Biomarkers; D006624:Hippocampus / Q000503:physiopathology; D006728:Hormones / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008032:Limbic System / Q000503:physiopathology; D008954:Models, Biological; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D013312:Stress, Physiological / Q000503:physiopathology
D015415:Biomarkers; D006728:Hormones; D006854:Hydrocortisone