Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy.

Gargi Banerjee,Ashley M Groves,Jamie Toombs,Michael P Lunn,Henrik Zetterberg,Gareth Ambler,Martha S Foiani,John C Dickson,Francesco Fraioli,David J Werring,Ashvini Keshavan,Nick C Fox,Ross W Paterson,Jonathan M Schott,Amanda Heslegrave

doi:10.3233/jad-191254

Abstract

Background:There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA).Objective:To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA.Methods:We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer’s disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service.Results:We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for Aβ38, Aβ40, Aβ42, and sAβPPβ. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF Aβ42, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an “AD-like” profile.Conclusion:CAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed.

Highlights

Sporadic amyloid-␤ (A␤) cerebral amyloid angiopathy (CAA) can be reliably diagnosed during life using the clinico-radiological Boston criteria [1, 2], but most of its associated imaging features are likely to be irreversible markers of late stage disease [3]
Our aim was to perform a detailed comparison of amyloid markers (A␤38, A␤40, A␤42, soluble amyloid-␤ protein precursor (sA␤PP)␣, and sA␤PP␤) and other markers studied in neurodegenerative disease (t-tau, p-tau, neurofilament light (NFL), soluble TREM2 (sTREM2), and neurogranin) in the cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD), CAA, and control (CS) participants in an exploratory hypothesis-generating study
All CAA patients had been clinically asymptomatic in the 6 months prior to their study visits

Summary

Introduction

Sporadic amyloid-␤ (A␤) cerebral amyloid angiopathy (CAA) can be reliably diagnosed during life using the clinico-radiological Boston criteria [1, 2], but most of its associated imaging features are likely to be irreversible markers of late stage disease [3]. There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-␤ (A␤) cerebral amyloid angiopathy (CAA). CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of A␤38, A␤40, A␤42, sA␤PP␣, and sA␤PP␤. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF A␤42, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an “AD-like” profile

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Discussion

Conclusion