Does Alzheimer's disease result from attempts at repair or protection after transient stress?
This review explores the data indicating that the initial production of amyloid-beta precursor protein and phosphorylated tau are associated with physiological mechanisms for repair or protection of neurons exposed to significant disturbances in homeostasis. Stimuli as diverse as head injury, inhaled anesthetic agents, stimulant drugs, and both physiological (restraint) and psychological stress (social isolation) have been shown to increase brain expression of amyloid-beta and hyperphosphorylated tau without accompanying neurodegeneration. This review aims to encompass these responses as indicators of normal physiological processes that, in the case of Alzheimer's disease, are either unable to successfully repair or protect vulnerable neuronal populations from eventual neurodegeneration, but that are necessary components of an integrated nervous system that would be more susceptible to pathology if such processes were blocked in an attempt to minimize or prevent future damage.
Bissette
Garth
G
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA. gbissette@psychiatry.umsmed.edu
D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D006259:Craniocerebral Trauma / Q000150:complications* / Q000378:metabolism; D003863:Depression / Q000150:complications*; D004195:Disease Models, Animal; D006213:Hallucinogens / Q000009:adverse effects; D006801:Humans; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects; D019636:Neurodegenerative Diseases / Q000150:complications* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000150:complications* / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D006213:Hallucinogens; D016875:tau Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine