Cerebrospinal Fluid Profile of Tau, Phosphorylated Tau, Aβ₄₂, and Aβ₄₀ in Probable Cerebral Amyloid Angiopathy

Article type: Research Article

Authors: Grangeon, Lou^{a; *} | Paquet, Claire^b | Guey, Stéphanie^c | Zarea, Aline^a | Martinaud, Olivier^d | Rotharmel, Maud^e | Maltête, David^a | Quillard-Muraine, Muriel^f | Nicolas, Gael^g | Charbonnier, Camille^g | Chabriat, Hugues^c | Wallon, David^a

Affiliations: [a] Normandie Univ, UNIROUEN, Inserm U1245 and CHURouen, Department of Neurology and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France | [b] CMRR Paris Nord AP-HP, Groupe Hospitalier Lariboisière Fernand-Widal Saint-Louis, INSERM, U942, Université Paris Diderot, Sorbonne Paris Cité, UMRS 942, France | [c] Department of Neurology, AP-HP, Groupe Hospitalier Lariboisière Fernand-Widal Saint-Louis, Paris, France | [d] Department of Neurology, Caen University Hospital, Caen, France | [e] Rouvray Hospital of Rouen, University Department of Psychiatry, France | [f] Laboratory of Biochemistry, CHU Rouen, Rouen France | [g] Normandie Univ, UNIROUEN, Inserm U1245 and CHU Rouen, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France

Correspondence: [*] Correspondence to: Lou Grangeon, MD, Department of Neurology, Rouen University Hospital, 76031 Rouen Cedex, France. Tel.: +33 2 32 88 82 94; Fax: +33 2 32 88 87 41; E-mail: lou.grangeon@chu-rouen.fr.

Abstract: Background:There is no consensus regarding the diagnostic value of cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers in cerebral amyloid angiopathy (CAA). Objective:To describe the CSF levels of Aβ42, Aβ40, total protein Tau, and phosphorylated-Tau (p-Tau) in a large series of probable CAA patients and to compare with AD patients in order to identify a specific pattern in CAA but also to look for correlations with the neuroimaging profile. Methods:We retrospectively included from 2 French centers probable CAA patients according to modified Boston criteria who underwent lumbar puncture (LP) with CSF AD biomarker quantifications. Two neurologists independently analyzed all MRI sequences. A logistic regression and Spearman’s correlation coefficient were used to identify correlation between MRI and CSF biomarkers in CAA. Results:We included 63 probable CAA and 27 AD patients. Among CAA 50.8% presented with decreased Aβ42 level associated with elevated p-Tau and/or Tau, 34.9% with isolated decreased Aβ42 level and 14.3% patients with normal Aβ42 level. Compared to AD, CAA showed lower levels of Tau (p = 0.008), p-Tau (p = 0.004), and Aβ40 (p = 0.001) but similar Aβ42 level (p = 0.07). No correlation between Aβ42 or Aβ40 levels and neuroimaging was found. Conclusion:CSF biomarkers may improve the accuracy of the modified Boston criteria with altered profile in 85% of the patients fulfilling revised Boston criteria for probable CAA. Aβ40 appears as an interesting selective biomarker in differential diagnosis.

Keywords: Aβ₄₂, Aβ₄₀, cerebral amyloid angiopathy, cerebrospinal fluid biomarker, intracerebral hemorrhage

DOI: 10.3233/JAD-215208

Journal: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 791-802, 2022