Amyloid‐βeta peptides in CSF and plasma discriminate cerebral amyloid angiopathy from controls. (December 2021)

• Record Type: Journal Article
• Authors: Verbeek, Marcel M.; de Kort, Anna M.; Wermer, Marieke J.H.; Marques, Tainá M.; Kersten, Iris; Schreuder, Floris H.B.M.; Klijn, Catharina J.M.; Stoops, Erik; Brinkmalm, Gunnar; Portelius, Erik; Gkanatsiou, Eleni; van Etten, Ellis; Rasing, Ingeborg
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.053858
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid‐beta (Abeta) peptides in the cerebral vasculature and has been associated with vascular dementia and intracerebral haemorrhages (ICH). Currently, the diagnosis of CAA is based on neuroimaging and includes the identification of lobar (micro‐)bleeds and cortical superficial siderosis. However, these MRI markers reflect only late‐stage manifestations and are therefore not suitable for an early diagnosis of CAA. We aimed to evaluate the diagnostic potential of the Abeta peptides AB1‐38, AB1‐40, AB1‐42, and AB1‐43 in cerebrospinal fluid (CSF) to discriminate (early) CAA from controls. Method: We used immunoassays to quantify AB1‐38, AB1‐40 and AB1‐42 in CSF and plasma and AB1‐43 only in CSF. CSF from sporadic CAA patients (n=28) and controls (n=40), and plasma from hereditary Dutch CAA (D‐CAA) patients (asymptomatic and symptomatic), sporadic CAA patients (n=129) and controls (n=99) were analyzed. Result: In CSF we found decreased levels of AB1‐38 ( p =0.03; AUC 0.64), AB1‐40 ( p =0.04; AUC 0.63), AB1‐42 ( p <0.0001, AUC 0.87) and AB1‐43 ( p <0.0001, AUC 0.92) in CAA patients compared to controls. In plasma we found significantly decreased levels of AB1‐38, AB1‐40 and AB1‐42 both in asymptomatic and symptomatic D‐CAA mutation carriers compared to controls. The concentrations of all Abeta peptides strongly correlated with each other (Spearman r >0.6, p <0.0001 for each comparison). Conclusion: Abeta peptides have strong biomarker potential for the diagnosis of (early)_CAA. Interestingly, our results indicate that AB1‐43, which has shown to be relatively low‐abundant in vascular amyloid deposits, has the highest diagnostic accuracy to discriminate CAA from controls. In addition, we show that CSF AB1‐38 levels are decreased in CAA compared to controls.