Tau protein and beta-amyloid(1-42) CSF levels in different phenotypes of Parkinson's disease.
ABSTRACT Parkinson's disease (PD) is a neurodegenerative disorder with highly heterogeneous clinical manifestations. This fact has prompted many attempts to divide PD patients into clinical subgroups. This could lead to a better recognition of pathogenesis, improving targeted treatment and the prognosis of PD patients. The aim of the present study was to obtain cerebrospinal fluid (CSF) samples in PD patients and to search for a relationship between neurodegenerative CSF markers (tau protein, beta-amyloid(1-42) and index tau protein/beta-amyloid(1-42)) and the clinical subtypes. PD patients were divided into three subgroups: early disease onset (EDO), tremor-dominant PD (TD-PD), and non-tremor dominant PD (NT-PD) according to the previously published classification. Neurodegenerative markers in the CSF were assessed in these three groups of patients suffering from PD (EDO-17, TD-15, NT-16 patients) and in a control group (CG) of 19 patients suffering from non-degenerative neurological diseases and 18 patients with Alzheimer's disease (AD). The NT-PD patients were found to have significantly higher levels of CSF tau protein and index tau/beta than the control subjects and other Parkinsonian subgroups, but no significant differences in these markers were found between AD and NT-PD patients. In the context of more rapid clinical progression and more pronounced neuropathological changes in the NT-PD patient group, our results corroborate the opinion that CSF level of tau protein may be regarded as a potential laboratory marker of the presence and severity of neurodegeneration.
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ABSTRACT: Neuronal dysfunction and degeneration are central events of a number of major diseases with significant unmet need. Neuronal dysfunction may not necessarily be the result of cell death, but may also be due to synaptic damage leading to impaired neuronal cell signaling or long-term potentiation. Once degeneration occurs, it is unclear whether axonal or synaptic loss comes first or whether this precedes neuronal cell death. In this review we summarize the pathophysiology of four major neurodegenerative diseases; Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig's disease) For each of these diseases, we describe how biochemical biomarkers are currently understood in relation to the pathophysiology and in terms of neuronal biology, and we discuss the clinical and diagnostic utility of these potential tools, which are at present limited. We discuss how markers may be used to drive drug development and clinical practice.Expert Review of Molecular Diagnostics 11/2013; 13(8):845-61. · 4.09 Impact Factor
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ABSTRACT: Parkinson disease is the second most common neurodegenerative disease after Alzheimer disease, and current demographic trends indicate a life-time risk approaching 4% and predict a doubling of prevalence by 2030. Strategies are being developed to apply recent advances in our understanding of the cause of Parkinson disease to the development of biomarkers that will enable the identification of at-risk individuals, enable early diagnosis and reflect the progression of disease. The latter will be particularly important for the testing of disease-modifying therapies. This review summarizes recent advances in Parkinson disease biomarker development. Recent reports continue to reflect the application of a variety of clinical, imaging or biochemical measurements, alone or in combination, to general Parkinson disease populations. Probably the most promising is the assay of alpha-synuclein in the diagnosis and evolution of Parkinson disease. At present, detection techniques are still being refined, but once accurate and reproducible assays are available, it will be important to define the relationship of these to early diagnosis and progression. Alpha-synuclein concentrations may also be modulated by certain disease-modifying agents in development and so may represent a measure of their efficacy. It has to be accepted that no single measure currently fulfils all the necessary criteria for a biomarker in Parkinson disease, but combinations of measures are more likely to deliver benefit. The Parkinson disease biomarker field is approaching a stage when certain combinations of clinical, imaging and biochemical measures may identify a proportion of individuals at risk for developing the disease. However, their general applicability may be limited. Attention is now turning to stratification of Parkinson disease into certain at-risk groups defined by genotype. The application of multimodal screening to these populations may be more rewarding in the short term.Current opinion in neurology 08/2013; 26(4):395-400. · 5.43 Impact Factor
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ABSTRACT: CSF biomarker studies were performed in 6 patients each with tremor-dominant (TD) and non-tremor-dominant (NT) Parkinson disease (PD) patients, 27 Alzheimer disease (AD) and 17 age-matched controls. In both NT-PD and AD patients total tau levels and the cortex tau/Aβ-42 were significantly increased compared to both TD-PD patients and controls (p < 0.01). These data in a small cohort confirm previous studies, corroborating the opinion that CSF levels of tau protein and the index total-tau/Aβ-42 may be potential markers of the severity of neurodegeneration in PD.Journal of Neural Transmission 11/2011; 119(4):455-6. · 3.05 Impact Factor