title: Differential Diagnosis of Dementia with High Levels of Cerebrospinal Fluid Tau Protein.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France.
authors.forename: Lou
authors.initials: L
authors.lastname: Grangeon
authors.affiliation: CMRR Paris Nord AP-HP, Groupe Hospitalier Lariboisière Fernand-Widal Saint-Louis, INSERM, U942, Université Paris Diderot, Sorbonne Paris Cité, UMRS 942, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Paquet
authors.affiliation: Univ. Lille, Inserm U1171, Memory centre and CNR-MAJ, CHU, Lille, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bombois
authors.affiliation: Laboratoire de biochimie, Rouen University Hospital and University of Rouen, Rouen France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Quillard-Muraine
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Martinaud
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bourre
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Lefaucheur
authors.affiliation: INSERM U1079, Normandy Centre for Genomic Medicine and Personalized Medicine, IRIB, Normandy University, CNR-MAJ, Rouen University Hospital, Rouen, France.|Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Nicolas
authors.affiliation: CMRR Paris Nord AP-HP, Groupe Hospitalier Lariboisière Fernand-Widal Saint-Louis, INSERM, U942, Université Paris Diderot, Sorbonne Paris Cité, UMRS 942, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Dumurgier
authors.affiliation: Department of Radiology, Rouen University Hospital, Rouen, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gerardin
authors.affiliation: Department of Neurophysiology, Rouen University Hospital, Rouen, France.
authors.forename: Mary
authors.initials: M
authors.lastname: Jan
authors.affiliation: Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, APHP, Inserm UMR-S 1144, Université Paris Descartes, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.affiliation: Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, APHP, Inserm UMR-S 1144, Université Paris Descartes, Paris, France.|APHP, HUPNVS, Hopital Beaujon, Service de Biochimie, Clichy, France.
authors.forename: Katell
authors.initials: K
authors.lastname: Peoc'h
authors.affiliation: CMRR Paris Nord AP-HP, Groupe Hospitalier Lariboisière Fernand-Widal Saint-Louis, INSERM, U942, Université Paris Diderot, Sorbonne Paris Cité, UMRS 942, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Hugon
authors.affiliation: Univ. Lille, Inserm U1171, Memory centre and CNR-MAJ, CHU, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pasquier
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France.
authors.forename: David
authors.initials: D
authors.lastname: Maltête
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France.|INSERM U1079, Normandy Centre for Genomic Medicine and Personalized Medicine, IRIB, Normandy University, CNR-MAJ, Rouen University Hospital, Rouen, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France.|INSERM U1079, Normandy Centre for Genomic Medicine and Personalized Medicine, IRIB, Normandy University, CNR-MAJ, Rouen University Hospital, Rouen, France.
authors.forename: David
authors.initials: D
authors.lastname: Wallon
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid*; D015140:Dementia, Vascular / Q000134:cerebrospinal fluid; D003937:Diagnosis, Differential; D005260:Female; D005602:France; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010766:Phosphorylation; D012189:Retrospective Studies; D012737:Sex Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins
keywords: Alzheimer’s disease; Creutzfeldt-Jakob disease; cerebrospinal fluid biomarker; dementia; tau