Journal
EXPERIMENTAL GERONTOLOGY
Volume 41, Issue 4, Pages 346-359Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2006.01.014
Keywords
Alzheimer's disease; postoperative cognitive dysfunction; beta-Amyloid Precursor Protein (APP); beta-Amyloid protein (A beta); anesthesia; apoptosis
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Funding
- NIA NIH HHS [P60 AG008812-15, K12 AG00294-17, AG 014713-07] Funding Source: Medline
- NIMH NIH HHS [MH 60009-03] Funding Source: Medline
- NINDS NIH HHS [K08 NS048140-01] Funding Source: Medline
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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 (A beta) generated from amyloidogenic processing of the beta-amyloid precursor protein (APP) plays a fundamental role in the AD neuropathogenesis. A beta is produced from APP by P-secretase, and then gamma-secretase complex, consisting of presenilins, nicastrin (NCSTN), APH-1 and PEN-2. Additionally, A beta clearance and APP adaptor proteins can contribute to AD neuropathogenesis via affecting A beta 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. (c) 2006 Elsevier Inc. All rights reserved.
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