Biomarkers in cerebrospinal fluid for synucleinopathies, tauopathies, and other neurodegenerative disorders.

The incidence of neurodegenerative disorders is increasing due to worldwide population aging. In general, sporadic forms account for 90% of total cases with neurodegenerative disorders and the reasons underlying initiation or progression of these diseases remain unknown for almost all disorders. To date, diagnosis is mainly based on clinical symptoms and neuroimaging, which is in many cases insufficient due to overlap in clinical symptoms among several neurodegenerative disorders. Therefore, postmortem neuropathologic confirmation remains the gold-standard diagnostic technique for many disorders. Biomarkers that could help in defining the clinical diagnosis, or predict disease progression and response to treatment, would therefore be very useful. In this chapter, we discuss potential biomarkers in cerebrospinal fluid studied in synucleinopathies, tauopathies, and other neurodegenerative disorders, and their possible application for clinical practice. Dementias are excluded in this analysis as these are discussed in Chapter 6.

SNCA Gene Polymorphism may Contribute to an Increased Risk of Alzheimer's Disease.

BACKGROUND: The purpose of this study is to elucidate the association between α-synuclein (SNCA) polymorphisms and the risk of Alzheimer's disease (AD). METHODS: The PCR-RFLP was applied to detect SNCA gene rs6532190, rs3775430, and rs10516846 polymorphisms in 98 AD patients and 105 healthy elderly. RESULTS: The GG frequency of rs10516846 was evidently increased in AD group than control group (P < 0.05). There was a significant difference in SNCA level between the AD and control groups (P < 0.01). In the AD group, the SNCA level in cerebrospinal fluid of GG (rs10516846) carriers was increased as compared with AA carriers (P < 0.05). The GG (rs10516846) frequency of the early-onset AD group is significantly higher than that of the late-onset AD group (P < 0.05). The frequency of rs3775430 GG was lower in the early-onset group than that in the late-onset group (0% vs. 16.7%). The SNCA level in cerebrospinal fluid of GG (rs10516846) carriers in the early-onset AD group is higher than that of AA carriers (P < 0.05). CONCLUSION: SNCA gene polymorphism may be associated with an increased risk of AD and GG genotype of rs10516846 and elevated SNCA level in CSF may increase the risk of early-onset AD.

Serum and cerebrospinal fluid urate levels in synucleinopathies versus tauopathies.

BACKGROUND: Low levels of serum urate are associated with a higher risk of Parkinson's disease (PD). Higher serum and cerebrospinal fluid (CSF) urate levels are associated with slower rates of clinical decline in PD and in multiple system atrophy (MSA). AIMS: To compare CSF and blood urate levels in healthy controls, patients with synucleinopathies and with tauopathies. METHODS: We investigated urate levels in serum and CSF from 18 healthy controls, 19 patients with synucleinopathies (six patients with PD and 13 with MSA), and 24 patients with tauopathies (18 with progressive supranuclear palsy and six with corticobasal degeneration). None of the patients were treated with dopaminergic medications. RESULTS: No significant differences were seen when comparing serum and CSF urate levels from controls across the parkinsonian diagnostic groups. However, in men, serum urate levels were significantly lower in the synucleinopathy group compared with the tauopathy group (P = 0.046), although with a broad overlap. CONCLUSION: Our study suggests that urate levels might provide new insights into the potential pathophysiological mechanisms underlying Parkinsonism and thereby contribute to the future management of these disorders.