Neurochemical biomarkers in the differential diagnosis of movement disorders

Abstract

In recent years, the neurochemical analysis of neuronal proteins in cerebrospinal fluid (CSF) has become increasingly accepted for the diagnosis of neurodegenerative dementia diseases such as Alzheimer's disease and Creutzfeldt-Jakob disease. CSF surrounds the central nervous system, and in the composition of CSF proteins one finds brain-specific proteins that are prioritized from blood-derived proteins. Levels of specific CSF proteins could be very promising biomarkers for central nervous system diseases. We need the development of more easily accessible biomarkers, in the blood. In neurodegenerative diseases with and without dementia, studies on CSF and blood proteins have investigated the usefulness of biomarkers in differential diagnosis. The clinical diagnoses of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration still rely mainly on clinical symptoms as defined by international classification criteria. In this article, we review CSF biomarkers in these movement disorders and discuss recent published reports on the neurochemical intra vitam diagnosis of neurodegenerative disorders (including recent CSF alpha-synuclein findings).

α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia

“…Several studies in neurodegenerative diseases have also failed to show a consistent correlation between increased serum ␣ -synuclein levels and the presence of disease symptoms/signs [El-Agnaf et al, 2006;Lee et al, 2006;Li et al, 2007;Mollenhauer and Trenkwalder, 2009]. Furthermore, an inverse correlation between CSF ␣ -synuclein levels and disease severity has been shown for patients with Alzheimer's disease and Parkinson's disease [Öhrfelt et al, 2009;Mollenhauer et al, 2008], suggesting the possibility that ␣ -synuclein levels correlate with synaptic integrity and thus show a decline over time with neurodegeneration.…”

CSF amyloid β 1-42 predicts cognitive decline in Parkinson disease

“…Decreased levels of A␤ have been demonstrated in CSF from patients with DLB compared to normal controls. 9,26 In patients with PDD, modest reductions in CSF A␤ have been shown compared to normal controls, 27,28 and in PD without dementia, A␤ 1-42 levels are not consistently reduced. 9 Increased CSF levels of total tau and p-tau 181p have been associated with impaired cognitive performance in patients with PD and PDD.…”

Immunology of the Lymphatic System

“…As discussed above, it would appear that a large fraction of the ISF drains through the subarachnoid space via adventitial perivascular channels (Casley-Smith et al 1978 ). Similar to the question of lymphatic uptake in humans, the issue of ISF-CSF communication in humans remains an open question, although it is interesting to note that CSF levels of brain proteins, which would require such communication, are commonly used as biomarkers in a number of dementia disorders (Mollenhauer and Trenkwalder 2009 ;Eller and Williams 2009 ;Frankfort et al 2008 ;Leinonen et al 2011 ).…”