Differential levels of alpha-synuclein, beta-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 alpha-synuclein, beta-amyloid42 (Abeta42) 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 alpha-synuclein gene (SNCA) duplication were also examined. Abeta and tau were quantified using an ELISA kit. A modified sandwich ELISA was developed which enables the sensitive quantification of CSF alpha-synuclein.


RESULTS
Total and phosphorylated tau levels as well as Abeta40/42 and tau/Abeta42 ratios were significantly higher in AD patients than in patients with DLB (p<0.01) and other dementias (p<0.01). CSF alpha-synuclein levels in DLB patients were significantly lower than those in patients with AD (p<0.05) and other dementias (p<0.01). CSF alpha-synuclein level correlated with the Abeta42 level in DLB patients (p=0.01, r=0.43). Two patients with SNCA duplication exhibited relatively low levels of CSF alpha-synuclein.


CONCLUSIONS
The study suggests that reduced levels of CSF alpha-synuclein in DLB may reflect the accumulation of alpha-synuclein with Lewy pathology in the brain and that quantification of CSF alpha-synuclein helps in the differentiation of DLB from AD and other dementias in combination with Abeta42 and tau analysis.
Kasuga
Kensaku
K
Department of Molecular Neuroscience, Brain Research Institute, Niigata University, Asahimachi 1-757, Chuo-ku, Niigata 951-8585, Japan.
Tokutake
Takayoshi
T
Ishikawa
Atsushi
A
Uchiyama
Tsuyoshi
T
Tokuda
Takahiko
T
Onodera
Osamu
O
Nishizawa
Masatoyo
M
Ikeuchi
Takeshi
T
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000235:genetics; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid* / Q000235:genetics*; D010641:Phenotype; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid* / Q000235:genetics*; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D016875:tau Proteins