Alzheimer's disease and post-operative cognitive dysfunction.
Alzheimer's disease (AD), an insidious and progressive neurodegenerative disorder accounting for the vast majority of dementia, is characterized by global cognitive decline and the robust accumulation of amyloid deposits and neurofibrillary tangles in the brain. This review article is based on the currently published literature regarding molecular studies of AD and the potential involvement of AD neuropathogenesis in post-operative cognitive dysfunction (POCD). Genetic evidence, confirmed by neuropathological and biochemical studies, indicates that excessive beta-amyloid protein (Abeta) generated from amyloidogenic processing of the beta-amyloid precursor protein (APP) plays a fundamental role in the AD neuropathogenesis. Abeta is produced from APP by beta-secretase, and then gamma-secretase complex, consisting of presenilins, nicastrin (NCSTN), APH-1 and PEN-2. Additionally, Abeta clearance and APP adaptor proteins can contribute to AD neuropathogenesis via affecting Abeta levels. Finally, cellular apoptosis may also be involved in AD neuropathogenesis. Surgery and anesthesia can cause cognitive disorders, especially in elderly patients. Even the molecular mechanisms underlying these disorders are largely unknown; several perioperative factors such as hypoxia, hypocapnia and anesthetics may be associated with AD and render POCD via trigging AD neuropathogenesis. More studies to assess the potential relationship between anesthesia/surgery and AD dementia are, therefore, urgently needed.
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114 16th Street M3725, Charlestown, MA 02129-4404, USA. zxie@partners.org
Zhongcong
Z
Xie
Rudolph E
RE
Tanzi
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000758:Anesthesia / Q000009:adverse effects; D017209:Apoptosis; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006935:Hypercapnia / Q000150:complications; D000860:Hypoxia / Q000150:complications; D011183:Postoperative Complications
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor