Differential Diagnosis of Dementia with High Levels of Cerebrospinal Fluid Tau Protein

Article type: Research Article

Authors: Grangeon, Lou^a | Paquet, Claire^b | Bombois, Stephanie^c | Quillard-Muraine, Muriel^d | Martinaud, Olivier^a | Bourre, Bertrand^a | Lefaucheur, Romain^a | Nicolas, Gaël^{e; f} | Dumurgier, Julien^b | Gerardin, Emmanuel^g | Jan, Mary^h | Laplanche, Jean-Louisⁱ | Peoc’h, Katell^{i; j} | Hugon, Jacques^b | Pasquier, Florence^c | Maltête, David^a | Hannequin, Didier^{a; e} | Wallon, David^{a; e; *} | the collaborators of the ePLM.fr group

Affiliations: [a] Department of Neurology, Rouen University Hospital, 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, Paris, France | [c] Univ. Lille, Inserm U1171, Memory centre and CNR-MAJ, CHU, Lille, France | [d] Laboratoire de biochimie, Rouen University Hospital and University of Rouen, Rouen France | [e] INSERM U1079, Normandy Centre for Genomic Medicine and Personalized Medicine, IRIB, Normandy University, CNR-MAJ, Rouen University Hospital, Rouen, France | [f] Department of Genetics, Rouen University Hospital, Rouen, France | [g] Department of Radiology, Rouen University Hospital, Rouen, France | [h] Department of Neurophysiology, Rouen University Hospital, Rouen, France | [i] Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, APHP, Inserm UMR-S 1144, Université Paris Descartes, Paris, France | [j] APHP, HUPNVS, Hopital Beaujon, Service de Biochimie, Clichy, France

Correspondence: [*] Correspondence to: Dr. David Wallon, Department of Neurology, Rouen University Hospital, 76031 Rouen, France. Tel.: +33 232 888 740; Fax: +33 232 888 741; E-mail: [email protected].

Abstract: Background:Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer’s disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses. Objective:Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p-Tau/Tau ratio to specify its ability to distinguish AD from CJD. Methods:Patients (n = 202) with CSF Tau levels over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria. Results:Patients were diagnosed with AD (n = 148, 73.2%), mixed dementia (n = 38, 18.8%), CJD, vascular dementia (n = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p < 0.0001). Conclusion:Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD.

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarker, Creutzfeldt-Jakob disease, dementia, tau

DOI: 10.3233/JAD-151111

Journal: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 905-913, 2016