Studies of the pathophysiological mechanisms in frontotemporal dementia by proteome analysis of CSF proteins

Comparative proteomic analysis of cerebrospinal fluid (CSF) proteins was employed for studies of the pathophysiological mechanisms in frontotemporal dementia (FTD). Two-dimensional gel electrophoresis and mass spectrometry were used for clinical screening of disease-influenced CSF proteins in 15 FTD patients compared to 12 controls. Six proteins were significantly altered in FTD compared to controls, including granin-like neuroendocrine precursor (proSAAS), pigment-epithelium derived factor (PEDF), retinol-binding protein (RBP), apoE, haptoglobin, and albumin. The levels of ProSAAS, PEDF, and RBP have not been shown earlier to be involved in the FTD pathology. Recently, we have also used proteomic analysis for studies of disease-influenced CSF proteins in Alzheimer's disease (AD) patients. The most clearly affected CSF proteins were the apolipoproteins in AD, compared to controls and FTD patients. ApoE seems to be influenced to a lesser degree in FTD compared to AD. Our data showed that several proteins involved in FTD pathology are not influenced in the CSF of AD patients, and vice versa, establishing differences in the pathophysiological mechanisms between FTD and AD, two of the most common neurodegenerative disorders.