CSF amyloid β38 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 β42 (Aβ42) 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 Aβ38, 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 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.


RESULTS
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%.


CONCLUSIONS
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.
Department of Old Age Psychiatry, Psychiatric Clinic, Stavanger University Hospital, Stavanger, Norway.
Ezra
E
Mulugeta
Elisabet
E
Londos
Clive
C
Ballard
Guido
G
Alves
Henrik
H
Zetterberg
Kaj
K
Blennow
Ragnhild
R
Skogseth
Lennart
L
Minthon
Dag
D
Aarsland
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D015331:Cohort Studies; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid* / Q000523:psychology; D008297:Male; D009483:Neuropsychological Tests; D009664:Norway; D010300:Parkinson Disease / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012372:ROC Curve; D015203:Reproducibility of Results; D012727:Sex Characteristics; D013548:Sweden; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078639:amyloid beta-protein (1-38); C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins