PMID- 24334212 OWN - NLM STAT- MEDLINE DCOM- 20141211 LR - 20220309 IS - 1878-4216 (Electronic) IS - 0278-5846 (Linking) VI - 50 DP - 2014 Apr 3 TI - GSK3beta, CREB, and BDNF in peripheral blood of patients with Alzheimer's disease and depression. PG - 83-93 LID - S0278-5846(13)00270-4 [pii] LID - 10.1016/j.pnpbp.2013.12.001 [doi] AB - BACKGROUND: Glycogen synthase kinase-3beta (GSK3beta), cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) play critical roles in neuronal survival, synaptic plasticity and memory and participate in the pathophysiology of both depressive disorder and Alzheimer's disease (AD). METHODS: This study was designed to determine the association of GSK3beta activity, CREB activity and BDNF concentration in peripheral blood of patients with AD with or without depressive symptoms and in depressive patients without AD. GSK3beta activity in platelets, CREB activity in lymphocytes and BDNF concentration in plasma, platelet-rich plasma or platelets were measured in 85 AD patients (36 of whom displayed co-morbid depressive symptoms), 65 non-AD patients with depressive disorder and 96 healthy controls. AD patients were clinically assessed for stage of dementia, cognitive impairment and severity of depressive symptoms. Depressive patients were clinically assessed for severity of depression. RESULTS: We observed increased CREB activity and GSK3beta activity in AD with depressive symptoms or in AD at mild stage of dementia. Decreased BDNF concentration was found in platelet-rich plasma of AD patients at moderate to severe stages of dementia or in AD without depressive symptoms. An association was revealed of the severity of cognitive impairment with the increase of GSK3beta in the platelets of AD patients with mild dementia. In depressive patients, a lower concentration of phosphorylated GSK3beta was associated with a higher severity of depression. Association was confirmed between severity of depression, CREB activation, and BDNF concentration in drug-naive depressive patients. CONCLUSION: Our data demonstrated that AD is accompanied by increased CREB activity in lymphocytes and a decreased concentration of BDNF in platelet-rich plasma. The decreased BDNF concentration appears to correlate with moderate to severe stages of dementia in AD. Observation of decreased phosphorylation of GSK3beta in platelets of both AD patients with depressive symptoms and depressive patients after treatment confirms the role of increased GSK3beta activity in the pathophysiology of both AD and depressive disorder. Associations were confirmed between AD and platelet GSK3beta activity, lymphocyte CREB activity and plasma BDNF. CREB activity and platelet BDNF concentration seems to be related to depressive disorder. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Platenik, Jan AU - Platenik J AD - Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Katerinska 32, 121 08 Prague 2, Czech Republic. FAU - Fisar, Zdenek AU - Fisar Z AD - Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic. Electronic address: zfisar@lf1.cuni.cz. FAU - Buchal, Richard AU - Buchal R AD - Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Katerinska 32, 121 08 Prague 2, Czech Republic. FAU - Jirak, Roman AU - Jirak R AD - Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic. FAU - Kitzlerova, Eva AU - Kitzlerova E AD - Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic. FAU - Zverova, Martina AU - Zverova M AD - Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic. FAU - Raboch, Jiri AU - Raboch J AD - Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131212 PL - England TA - Prog Neuropsychopharmacol Biol Psychiatry JT - Progress in neuro-psychopharmacology & biological psychiatry JID - 8211617 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (CREBBP protein, human) RN - EC 2.7.11.1 (GSK3B protein, human) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) SB - IM MH - Aged MH - Alzheimer Disease/*blood/*complications/psychology MH - Brain-Derived Neurotrophic Factor/*blood MH - CREB-Binding Protein/*blood MH - Case-Control Studies MH - Depression/*blood/*complications/psychology MH - Female MH - Glycogen Synthase Kinase 3/*blood MH - Glycogen Synthase Kinase 3 beta MH - Humans MH - Male MH - Middle Aged MH - Neuropsychological Tests MH - Psychiatric Status Rating Scales OTO - NOTNLM OT - Alzheimer's disease OT - BDNF OT - CREB OT - Depressive disorder OT - GSK3beta EDAT- 2013/12/18 06:00 MHDA- 2014/12/17 06:00 CRDT- 2013/12/17 06:00 PHST- 2013/07/24 00:00 [received] PHST- 2013/11/20 00:00 [revised] PHST- 2013/12/02 00:00 [accepted] PHST- 2013/12/17 06:00 [entrez] PHST- 2013/12/18 06:00 [pubmed] PHST- 2014/12/17 06:00 [medline] AID - S0278-5846(13)00270-4 [pii] AID - 10.1016/j.pnpbp.2013.12.001 [doi] PST - ppublish SO - Prog Neuropsychopharmacol Biol Psychiatry. 2014 Apr 3;50:83-93. doi: 10.1016/j.pnpbp.2013.12.001. Epub 2013 Dec 12.