Abstract
Background: Alzheimer's disease (AD) is one of the most pressing and difficult to diagnose unmet diseases confronting industrialized countries. It is characterized by the appearance in the post mortem autopsied AD brain of amyloid plaques containing Aβ42 and paired helical filaments in neurofibrillary tangles with hyperphosphorylated tau. Objective: To investigate the potential of proteomics approaches for AD diagnosis. Methods: This reviews focuses on studies of the altered phosphorylation of tau and other proteins as detected in brain biopsy, cerebral spinal fluid (CSF) and blood samples. Results/conclusion: Detection of decreased Aβ42, and increased total and hyperphosphorylated tau in CSF from AD patients can provide a fairly reliable diagnosis. Furthermore, very recent studies have demonstrated altered levels of cytokines in plasma and differential gene expression and protein phosphorylation in peripheral blood mononuclear cells from AD patients. Identification of the roles of these proteins may provide valuable insights into the underlying molecular pathology of AD and possible sites for therapeutic intervention.
Acknowledgements
The author wishes to acknowledge the contributions of several collaborators. These include H Feldman at the University of British Columbia, H Akatsu (Choju Medical Centre in Fukushimura Hospital in Toyahashi City, Japan) and J Götz (Brain & Mind Research Institute at the University of Sydney, Australia).