CSF amyloid β38 as a novel diagnostic marker for dementia with Lewy bodies

The clinical distinction between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is sometimes difficult, particularly in mild cases. Although CSF markers such as amyloid β42 (Aβ42) and P-tau can distinguish between AD and normal controls, their ability to distinguish between AD and DLB is not adequate.

This study aims to investigate whether CSF markers, in particular levels of Aβ38, can differentiate between mild AD and DLB.

85 individuals were included after standardised diagnostic procedures: 30 diagnosed as probable AD, 23 probable DLB, 20 probable Parkinson's disease dementia and 12 non-demented control subjects. CSF levels of Aβ38, Aβ40 and Aβ42 were determined using commercially available ultra-sensitive multi-array kit assay (MSD) for human Aβ peptides. Total tau (T-tau) and phosphorylated tau (P-tau) were analysed using ELISA (Innotest). In addition, combinations (Aβ42/Aβ38, Aβ42/Aβ40, Aβ42/P-tau and Aβ42/Aβ38/P-tau) were assessed.

Significant between group differences were found for all CSF measures, and all except Aβ40, Aβ42 and Aβ42/P-tau differed between AD and DLB. The Aβ42/Aβ38 ratio was the measure that best discriminated between AD and DLB (AUC 0.765; p<0.005), with a sensitivity of 78% and a specificity of 67%.

This study suggests that the level of Aβ38 can potentially contribute in the diagnostic distinction between AD and DLB when combined with Aβ42. Single measures had low diagnostic accuracy, suggesting that developing a panel of markers is the most promising strategy. Studies with independent and larger samples and a priori cut-offs are needed to test this hypothesis.