Peripheral expression of key regulatory kinases in Alzheimer's disease and Parkinson's disease
Received 8 June 2009; received in revised form 27 October 2009; accepted 7 January 2010. published online 27 January 2010. Corrected Proof
Abstract
Alteration of key regulatory kinases may cause aberrant protein phosphorylation and aggregation in Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we investigated expression and phosphorylation status of glycogen synthase kinase 3 (GSK-3), protein kinase B (Akt) and tau protein in peripheral blood lymphocytes of 20 AD, 25 PD patients and 20 healthy controls.
GSK-3 was increased in AD and PD patients. In these latter, GSK-3 levels were positively correlated with daily l-Dopa intake. Phosphorylated Akt expression was augmented in both groups; total Akt levels were increased only in AD patients and were positively correlated with disease duration and severity. Total and phosphorylated tau were increased only in AD, with phospho-tau levels being positively correlated with levels of total tau, Akt, and disease duration. No correlations between protein levels and clinical variables were found in PD patients.
Investigation of peripheral changes in the expression of specific kinases may, therefore, lead to the development of innovative biomarkers of neurodegeneration, particularly for AD.
aInterdepartmental Research Center for Parkinson's Disease, IRCCS Neurological Institute “C. Mondino”, Via Mondino 2, 27100 Pavia (PV), Italy
bLaboratory of Experimental Neurobiology, IRCCS Neurological Institute “C. Mondino”, Pavia, Italy
cIRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy
dDept. of Clinical Medicine, University of Insubria, Varese/Neurorehabilitation and Movement Disorders Unit, IRCCS Fondazione S. Maugeri, Tradate, Italy
eChair of Neurology, University of Rome “La Sapienza”, Rome, Italy