Decreased CSF Levels of ß-Amyloid in Patients With Cortical Superficial Siderosis.

Cihan Catak,Alexander Krebs,Christian Opherk,Jennifer Linn,Rainer Malik,Frank A Wollenweber,Marco Düring,Marialuisa Zedde,Anna Seegerer,Vivian Soric,Daniel Janowitz

doi:10.3389/fneur.2019.00439

Abstract

Background: Cortical superficial siderosis (cSS) represents a key neuroimaging marker of cerebral amyloid angiopathy (CAA) that is associated with intracranial hemorrhages and cognitive impairment. Nevertheless, the association between cSS and core cerebrospinal fluid (CSF) biomarkers for dementia remain unclear.Methods: One hundred and one patients with probable (79%, 80/101) or possible (21%, 21/101) CAA according to the modified Boston criteria and mild cognitive impairment according to Petersen criteria were prospectively included between 2011 and 2016. CSF analyses of ß-amyloid 42, ß-amyloid 40, total tau and phosphorylated tau were performed using sandwich-type enzyme-linked immunosorbent-assay. All patients received MRI and Mini-Mental-State Examination (MMSE). Logistic regression analysis was used to adjust for possible confounders.Results: cSS was present in 61% (62/101). Of those, 53% (33/62) had disseminated cSS and 47% (29/62) focal cSS. ß-amyloid 42 was lower in patients with cSS than in patients without cSS (OR 0.2; 95% CI 0.08–0.6; p = 0.0052) and lower in patients with disseminated cSS than in those with focal cSS (OR 0.02; 95% CI 0.003–0.2; p = 0.00057). Presence of cSS had no association with regard to ß-amyloid 40, total tau and phosphorylated tau.Conclusions: Our results demonstrate that the presence and extent of cSS are associated with reduced CSF ß-amyloid 42 levels. Further studies are needed to investigate the underlying mechanisms of this association.

Highlights

Cerebral amyloid angiopathy (CAA)—characterized by the deposition of ß-amyloid in the walls of leptomeningeal vessels—is a common cerebral small vessel disease and a major cause of intracerebral hemorrhage in the elderly [1,2,3]
Patients with and without Cortical superficial siderosis (cSS) were well balanced with regard to age, sex, and cardiovascular risk factors
CAA patients with cSS had numerically lower median Mini-Mental State Examination (MMSE) values than CAA patients without cSS (23 vs. 27, Table 1). This difference did not reach statistical significance, neither without adjustment (0.4), nor in a model adjusting for sex, age and cardiovascular risk factors (p = 0.05) nor in a model adjusting for hypertension only (p = 0.1)

Summary

Introduction

Cerebral amyloid angiopathy (CAA)—characterized by the deposition of ß-amyloid in the walls of leptomeningeal vessels—is a common cerebral small vessel disease and a major cause of intracerebral hemorrhage in the elderly [1,2,3]. It has become evident that CAA is associated with cognitive impairment [4]. CSF biomarkers that are typically altered in AD [ß-amyloid 42 (Aß42), ß-amyloid 40 (Aß40), total tau (t-tau) and phosphorylated tau (p-tau)] may offer another approach to understand underlying mechanisms and courses of patients with CAA [6]. Cortical superficial siderosis (cSS) represents a key neuroimaging marker of cerebral amyloid angiopathy (CAA) that is associated with intracranial hemorrhages and cognitive impairment. The association between cSS and core cerebrospinal fluid (CSF) biomarkers for dementia remain unclear

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Discussion

Conclusion