Diagnostic Value of Cerebrospinal Fluid Biomarkers (Phospho-Tau181, total-Tau, Aβ42, and Aβ40) in Prodromal Stage of Alzheimer’s Disease and Dementia with Lewy Bodies

Abstract

We have shown that at the prodromal stage the DLB patients had no pathological profile. Consequently, CSF AD biomarkers are extremely useful for differentiating AD from DLB patients particularly at this stage when the clinical diagnosis is difficult. Thus, these results open up new perspectives on the interpretation of AD biomarkers in DLB.

Cerebrospinal fluid Alzheimer biomarkers can be useful for discriminating dementia with Lewy bodies from Alzheimer’s disease at the prodromal stage

“…It would be interesting to include, in future studies, groups of patients with comorbidity in order to be closer to the ‘real life’ diagnosis conditions. Nevertheless, concerning the AD diagnosis, the CSF analysis in patients with AD at either the prodromal or demented stage was in line with our previous results,20 and the literature and so confirms the quality of the clinical diagnosis. Concerning DLB diagnosis, given the excellent specificity (96%–98%) of the McKeith criteria,3 it seems likely that the patients in our DLB group were indeed correctly diagnosed.…”

“…In this study, the distribution of patients by number of pathological biomarkers differed from that of our previous work 20. This discrepancy may be partially explained by the different cut-offs used in the previous study and the multicentric design of the present study.…”

“…CSF Aβ40 levels in the different groups showed the same variations as in our previous, monocentric study,20 that is, Aβ40 levels slightly though not significantly decreased in patients with DLB-d in comparison with patients with pro-DLB and CS. Of note, the CSF Aβ40 increase in patients with pro-AD coupled with the slight decrease in CSF Aβ40 in patients with DLB-d means that this biomarker was a little more discriminating than Aβ42, whatever the stage of AD and DLB (AUC=0.80 (Aβ40) and AUC=0.76 (Aβ42) for prodromal groups and AUC=0.72 (Aβ40) and AUC=0.64 (Aβ42) for demented groups).…”

“…Overall, the literature suggests that there is no increase of CSF tau and phospho-Tau 181 levels in DLB 18 19. Several studies have described a decrease of CSF Aβ42 in patients with DLB; however, this decrease appears only belatedly, at the stage of dementia, as we described previously 20. Moreover, CSF Aβ40 appears to be decreased in patients with DLB compared with AD,19 21 22 making the Aβ42/Aβ40 ratio very interesting for the differential diagnosis between these two diseases 20 21.…”

Long-term cognitive outcome of Alzheimer’s disease and dementia with Lewy bodies: dual disease is worse

“…In the same way, if the first diagnosis was DLB (21%), the search for AD had to be done, particularly if on neuropsychological tests a memory storage deficit was found. In this situation, hippocampal atrophy raised interest in arguing for an AD diagnosis, but cerebrospinal fluid (CSF) analysis was clearly of importance [23]. …”