Cerebrospinal fluid biomarkers in dementia with Lewy bodies

Abstract

Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative disease of the aged after Alzheimer Disease (AD). However, DLB and AD pathology commonly coexist to some degree. Of cases meeting pathological criteria for DLB, 90% have some AD pathology. Of cases meeting pathological criteria for AD, as many as one third have some Lewy Bodies. While cerebrospinal fluid (CSF) biomarkers are increasingly used in diagnosis of Alzheimer's Disease, the CSF profile of other neurodegenerative diseases such as DLB is less established. Moreover, the pathoetiologic bases for the CSF biomarkers is not well established. Here we present CSF data on a retrospective sample of 101 cases with AD (N=80) or DLB (N=21). DLB was defined clinically, regardless of whether there was suspected concomitant AD pathology. CSF biomarkers included beta-amyloid42 (AB42), total tau, and phosphorylated tau (p-tau), and are expressed in units of pg/ml. Total tau was measured by two different methods, which differed by a conversion factor, but showed strong linear correlation (r = 0.85). Statistical comparisons used ANOVA analysis using IBM SPSS 19. This research was approved by the Columbia University Institutional Review Board. Cases with DLB and AD did not significantly differ with respect to CSF AB42, both showing lower than normal levels of AB42 (DLB 381 ± 185 vs. AD 338 ±193; p > 0.05). However cases with DLB showed markedly lower levels than cases with AD for both tau (DLB 288 ± 183 vs. AD 573 ± 401; p=0.002), and p-tau (DLB 39.5 ± 18.2 vs. AD 73.1 ± 36.2; p=0.001). Tau and p-tau were within normal range in DLB, but elevated in AD. CSF biomarkers in DLB show similar lowered values of AB42 as in AD, but do not show the characteristic elevated levels of tau and p-tau seen in AD. This dissociation cannot be explained simply by either AD concomitance or discordance. One possible explanation is that concomitant AD pathology in DLB cases predominantly involves beta-amyloid containing plaques, rather than tangles, but an alternative explanation presented is that the lowered AB42 in DLB relates more to synaptic dysfunction, present in both disorders.