CSF amyloid beta 38 as a novel diagnostic marker for dementia with Lewy bodies

Background 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 beta 42 (A beta 42) and P-tau can distinguish between AD and normal controls, their ability to distinguish between AD and DLB is not adequate. Objective This study aims to investigate whether CSF markers, in particular levels of A beta 38, can differentiate between mild AD and DLB. Methods 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 A beta 38, A beta 40 and A beta 42 were determined using commercially available ultra-sensitive multi-array kit assay (MSD) for human A beta peptides. Total tau (T-tau) and phosphorylated tau (P-tau) were analysed using ELISA (Innotest). In addition, combinations (A beta 42/A beta 38, A beta 42/A beta 40, A beta 42/P-tau and A beta 42/A beta 38/P-tau) were assessed. Results Significant between group differences were found for all CSF measures, and all except A beta 40, A beta 42 and A beta 42/P-tau differed between AD and DLB. The A beta 42/A beta 38 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%. Conclusion This study suggests that the level of A beta 38 can potentially contribute in the diagnostic distinction between AD and DLB when combined with A beta 42. 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.