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Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer's disease.
J Psychiatr Res. 2011 Feb; 45(2):220-4.JP

Abstract

The disruption of glycogen synthase kinase 3-beta (GSK3B) homeostasis has implications in the pathophysiology of neuropsychiatric disorders, namely Alzheimer's disease (AD). GSK3B activity is increased within the AD brain, favoring the hyperphosphorylation of microtubule-associated protein Tau and the formation of neurofibrillary tangles. Such abnormality has also been detected in leukocytes of patients with cognitive disorders. The aim of the present study was to determine the expression of total and phosphorylated GSK3B at protein level in platelets of older adults with varying degrees of cognitive impairment, and to compare GSK3B activity in patients with AD, mild cognitive impairment (MCI) and healthy controls. Sixty-nine older adults were included (24 patients with mild to moderate AD, 22 patients with amnestic MCI and 23 elderly controls). The expression of platelet GSK3B (total- and Ser-9 phosphorylated GSK3B) was determined by Western blot. GSK3B activity was indirectly assessed by means of the proportion between phospho-GSK3B to total GSK3B (GSK3B ratio), the former representing the inactive form of the enzyme. Ser-9 phosphorylated GSK3B was significantly reduced in patients with MCI and AD as compared to controls (p=0.04). Platelet GSK3B ratio was significantly decreased in patients with MCI and AD (p=0.04), and positively correlated with scores on memory tests (r=0.298, p=0.01). In conclusion, we corroborate previous evidence of increased GSK activity in peripheral tissues of patients with MCI and AD, and further propose that platelet GSK may be an alternative peripheral biomarker of this abnormality, provided samples are adequately handled in order to preclude platelet activation.

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Authors+Show Affiliations

Forlenza OV
Laboratory of Neuroscience (LIM 27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010 São Paulo, SP, Brazil. forlenza@usp.br
Torres CA
No affiliation info available
Talib LL
No affiliation info available
de Paula VJ
No affiliation info available
Joaquim HP
No affiliation info available
Diniz BS
No affiliation info available
Gattaz WF
No affiliation info available

MeSH

AgedAged, 80 and overAlzheimer DiseaseAnalysis of VarianceBlood PlateletsCognition DisordersFemaleGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansMaleMental Status ScheduleSerine

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20576277

Citation

Forlenza, Orestes V., et al. "Increased Platelet GSK3B Activity in Patients With Mild Cognitive Impairment and Alzheimer's Disease." Journal of Psychiatric Research, vol. 45, no. 2, 2011, pp. 220-4.
Forlenza OV, Torres CA, Talib LL, et al. Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer's disease. J Psychiatr Res. 2011;45(2):220-4.
Forlenza, O. V., Torres, C. A., Talib, L. L., de Paula, V. J., Joaquim, H. P., Diniz, B. S., & Gattaz, W. F. (2011). Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer's disease. Journal of Psychiatric Research, 45(2), 220-4. https://doi.org/10.1016/j.jpsychires.2010.06.002
Forlenza OV, et al. Increased Platelet GSK3B Activity in Patients With Mild Cognitive Impairment and Alzheimer's Disease. J Psychiatr Res. 2011;45(2):220-4. PubMed PMID: 20576277.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer's disease. AU - Forlenza,Orestes V, AU - Torres,Carolina A, AU - Talib,Leda L, AU - de Paula,Vanessa J, AU - Joaquim,Helena P G, AU - Diniz,Breno S, AU - Gattaz,Wagner F, Y1 - 2010/06/23/ PY - 2010/03/09/received PY - 2010/05/25/revised PY - 2010/06/01/accepted PY - 2010/6/26/entrez PY - 2010/6/26/pubmed PY - 2011/4/26/medline SP - 220 EP - 4 JF - Journal of psychiatric research JO - J Psychiatr Res VL - 45 IS - 2 N2 - The disruption of glycogen synthase kinase 3-beta (GSK3B) homeostasis has implications in the pathophysiology of neuropsychiatric disorders, namely Alzheimer's disease (AD). GSK3B activity is increased within the AD brain, favoring the hyperphosphorylation of microtubule-associated protein Tau and the formation of neurofibrillary tangles. Such abnormality has also been detected in leukocytes of patients with cognitive disorders. The aim of the present study was to determine the expression of total and phosphorylated GSK3B at protein level in platelets of older adults with varying degrees of cognitive impairment, and to compare GSK3B activity in patients with AD, mild cognitive impairment (MCI) and healthy controls. Sixty-nine older adults were included (24 patients with mild to moderate AD, 22 patients with amnestic MCI and 23 elderly controls). The expression of platelet GSK3B (total- and Ser-9 phosphorylated GSK3B) was determined by Western blot. GSK3B activity was indirectly assessed by means of the proportion between phospho-GSK3B to total GSK3B (GSK3B ratio), the former representing the inactive form of the enzyme. Ser-9 phosphorylated GSK3B was significantly reduced in patients with MCI and AD as compared to controls (p=0.04). Platelet GSK3B ratio was significantly decreased in patients with MCI and AD (p=0.04), and positively correlated with scores on memory tests (r=0.298, p=0.01). In conclusion, we corroborate previous evidence of increased GSK activity in peripheral tissues of patients with MCI and AD, and further propose that platelet GSK may be an alternative peripheral biomarker of this abnormality, provided samples are adequately handled in order to preclude platelet activation. SN - 1879-1379 UR - https://www.unboundmedicine.com/medline/citation/20576277/Increased_platelet_GSK3B_activity_in_patients_with_mild_cognitive_impairment_and_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3956(10)00180-9 DB - PRIME DP - Unbound Medicine ER -