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Differential levels of α-synuclein, β-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer's disease


Background The clinical diagnosis of dementia with Lewy bodies (DLB) is made on the basis of consensus criteria; however, the sensitivity of the criteria is relatively low. There are no generally accepted biomarkers to distinguish DLB from other dementias. Here the utility of quantification of α-synuclein, β-amyloid42 (Aβ42) and tau in the CSF of patients with DLB, Alzheimer's disease (AD) and other dementias was examined.

Methods 86 patients were divided into three age and sex matched groups: DLB (n=34), AD (n=31) and other dementias (n=21). Two patients with α-synuclein gene (SNCA) duplication were also examined. Aβ and tau were quantified using an ELISA kit. A modified sandwich ELISA was developed which enables the sensitive quantification of CSF α-synuclein.

Results Total and phosphorylated tau levels as well as Aβ40/42 and tau/Aβ42 ratios were significantly higher in AD patients than in patients with DLB (p<0.01) and other dementias (p<0.01). CSF α-synuclein levels in DLB patients were significantly lower than those in patients with AD (p<0.05) and other dementias (p<0.01). CSF α-synuclein level correlated with the Aβ42 level in DLB patients (p=0.01, r=0.43). Two patients with SNCA duplication exhibited relatively low levels of CSF α-synuclein.

Conclusions The study suggests that reduced levels of CSF α-synuclein in DLB may reflect the accumulation of α-synuclein with Lewy pathology in the brain and that quantification of CSF α-synuclein helps in the differentiation of DLB from AD and other dementias in combination with Aβ42 and tau analysis.

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