Interest of CSF biomarker analysis in possible cerebral amyloid angiopathy cases defined by the modified Boston criteria

Abstract

According to the modified Boston criteria, cerebral amyloid angiopathy (CAA) can present with lobar hematoma (LH) or superficial siderosis (SS). Recently, decreased CSF β-amyloid peptide 40 and 42 (Aβ40; Aβ42) and increased total and phosphorylated tau (t-tau; p-tau) concentrations have been described in CAA presenting with LH. Our aim was to analyze CSF biomarkers as a diagnostic tool for CAA according to the modified Boston criteria. We prospectively included patients with possible or probable CAA according to the modified Boston criteria. CSF was analyzed for t-tau, p-tau, Aβ42, and Aβ40. Data were compared with AD patients (n = 42) and controls (n = 14). Thirteen CAA patients were included, nine presenting with LH and four with SS. T-tau and p-tau levels in CAA were higher than controls, but lower than in AD. Differences in t-tau and p-tau levels between CAA versus controls and AD were all significant apart of the CAA p-tau levels comparison with controls. Aβ42 levels in CAA were significantly lower than in controls, and slightly higher than in AD, though non-significantly. Aβ40 levels in CAA were non-significantly lower than in controls, and significantly lower than in AD. Combining the findings of our study and the earlier report, we confirm that patients with suspected CAA have significantly different values for t-tau, Aβ42, Aβ42/t-tau, and Aβ40. Especially Aβ40 levels seem to be of clinical interest to differentiate CAA from AD. CSF biomarkers have to be analyzed in a larger number of CAA patients, and compared to patients with other disorders causing LH or SS.

β-Amyloid in CSF

“…21 Two previous studies in patients with sporadic CAA also demonstrated decreased CSF Ab 40 and Ab 42 levels. 10,11 However, in this study, the reduction in Ab 40 and Ab 42 was more pronounced, most likely because of the more severe phenotype of HCHWA-D. 22 Reduction in both CSF Ab 40 and 8 Our data hinted at the possibility that presymptomatic patients had relatively greater reductions in Ab 42 (55% of control values) than Ab 40 (75% of control values; figure 1 and table 2). This observation (which will require larger numbers of participants to confirm) likely relates to reports that in the process of Ab accumulation in the vessel wall, Ab 42 deposits earlier than Ab 40 .…”

“…9 In patients with sCAA with advanced vascular damage, decreased CSF Ab 42 and Ab 40 and mildly elevated t-tau and p-tau concentrations have been found. 10,11 We aimed to find biomarkers of the earliest, potentially reversible phases of CAA. We investigated whether altered CSF levels of Ab and tau species are detectable in presymptomatic and symptomatic hereditary CAA mutation carriers.…”

“…Previous studies showed mildly increased levels of tau species in participants with sCAA compared with controls, although the levels were lower than in participants with Alzheimer disease. 10,11 In Alzheimer disease, elevated CSF t-tau and p-tau 181 concentrations are presumably related to the formation of neurofibrillary tangles, although elevated tau species also might represent a nonspecific axonal injury. 32 The finding of elevated CSF tau levels in patients with sCAA might represent mixed CAA and Alzheimer pathology.…”

The overlap between vascular disease and Alzheimer’s disease - lessons from pathology

“…Correlations of these criteria with post-mortem neuropathological findings indicate that the diagnosis of probable CAA-related hemorrhage can be made intra vitam with high accuracy [102]-[105]. In addition to the presence of superficial siderosis, cerebral microbleeds, cortical microinfarcts, and hypointensities in MRI images [106]-[109], the use of Pittsburgh Compound-B (PiB)-positron emission tomography (PET) is useful in detecting CAA intra vitam [110],[111], and a significant decrease of both Aβ-40 and Aβ-42 in cerebrospinal fluid (CSF) may prove useful in the diagnosis of CAA [112],[113], while in AD, Aβ-42 but not Aβ-40 are significantly decreased [114]. …”

Background and distribution of lobar microbleeds in cognitive dysfunction

“…Second, we did not investigate Apo E genotype, which influences the spatial distribution of CMBs (Loehrer et al., 2014). Finally, we did not examine useful biomarkers for vascular amyloid deposition, including amyloid imaging and Aβ 40 and Aβ 42 values in cerebrospinal fluid (Dierksen et al., 2010; Renald et al., 2012). However, we think that these data are an essential first step to understanding the clinical implications of differences between SL‐CMBs and M‐CMBs.…”