BACKGROUND: Although epidemiological, clinical, and experimental evidence indicates that the inducible isoform of cyclo-oxygenase (COX-2) may be involved in the pathogenesis of several neurodegenerative disorders, the mechanisms whereby COX-2 contributes to Alzheimer's disease are largely unknown. OBJECTIVE: To undertake a longitudinal study of CSF levels of a major product of COX activity, prostaglandin E2 (PGE2), in relation to cognitive decline and survival in patients with Alzheimer's disease. METHODS: CSF PGE2 was measured on at least three annual visits in 35 controls and 33 Alzheimer patients (26 necropsy confirmed) who completed the Cambridge cognitive assessment (CAMCOG). RESULTS: Compared with controls, CSF PGE2 was higher in patients with mild memory impairment, but lower in those with more advanced Alzheimer's disease. The median survival time of patients with higher initial PGE2 levels was five years longer than those with lower levels. CONCLUSIONS: COX activity in Alzheimer's disease varies with stage of the disease. PGE2 levels correlate positively with patient survival. These findings suggest that inhibition of COX activity does not represent a major target for the pharmacological treatment of Alzheimer's disease.
BACKGROUND: Although epidemiological, clinical, and experimental evidence indicates that the inducible isoform of cyclo-oxygenase (COX-2) may be involved in the pathogenesis of several neurodegenerative disorders, the mechanisms whereby COX-2 contributes to Alzheimer's disease are largely unknown. OBJECTIVE: To undertake a longitudinal study of CSF levels of a major product of COX activity, prostaglandin E2 (PGE2), in relation to cognitive decline and survival in patients with Alzheimer's disease. METHODS:CSFPGE2 was measured on at least three annual visits in 35 controls and 33 Alzheimerpatients (26 necropsy confirmed) who completed the Cambridge cognitive assessment (CAMCOG). RESULTS: Compared with controls, CSFPGE2 was higher in patients with mild memory impairment, but lower in those with more advanced Alzheimer's disease. The median survival time of patients with higher initial PGE2 levels was five years longer than those with lower levels. CONCLUSIONS: COX activity in Alzheimer's disease varies with stage of the disease. PGE2 levels correlate positively with patient survival. These findings suggest that inhibition of COX activity does not represent a major target for the pharmacological treatment of Alzheimer's disease.
Authors: L Minghetti; F Cardone; A Greco; M Puopolo; G Levi; A J E Green; R Knight; M Pocchiari Journal: Neurology Date: 2002-01-08 Impact factor: 9.910
Authors: T J Montine; K R Sidell; B C Crews; W R Markesbery; L J Marnett; L J Roberts; J D Morrow Journal: Neurology Date: 1999-10-22 Impact factor: 9.910
Authors: L Minghetti; A Greco; F Cardone; M Puopolo; A Ladogana; S Almonti; C Cunningham; V H Perry; M Pocchiari; G Levi Journal: J Neuropathol Exp Neurol Date: 2000-10 Impact factor: 3.685
Authors: Jeroen J M Hoozemans; Martina K Brückner; Annemieke J M Rozemuller; Robert Veerhuis; Piet Eikelenboom; Thomas Arendt Journal: J Neuropathol Exp Neurol Date: 2002-08 Impact factor: 3.685
Authors: Jenny U Johansson; Nathaniel S Woodling; Qian Wang; Maharshi Panchal; Xibin Liang; Angel Trueba-Saiz; Holden D Brown; Siddhita D Mhatre; Taylor Loui; Katrin I Andreasson Journal: J Clin Invest Date: 2014-12-08 Impact factor: 14.808
Authors: Nathaniel S Woodling; Damien Colas; Qian Wang; Paras Minhas; Maharshi Panchal; Xibin Liang; Siddhita D Mhatre; Holden Brown; Novie Ko; Irene Zagol-Ikapitte; Marieke van der Hart; Taline V Khroyan; Bayarsaikhan Chuluun; Prachi G Priyam; Ginger L Milne; Arash Rassoulpour; Olivier Boutaud; Amy B Manning-Boğ; H Craig Heller; Katrin I Andreasson Journal: Brain Date: 2016-05-13 Impact factor: 13.501