Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's disease from cortical dementias

Leonardo Cruz de Souza (1, 2) , Foudil Lamari (2) , Serge Belliard (3) , Claude Jardel (2) , Caroline Houillier (2) , Raphael de Paz (2) , Bruno Dubois (1, 2) , Marie Sarazin (1, 2)

1 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
2 CHU Pitié-Salpêtrière [AP-HP]
3 Service de Neurologie [Rennes] = Neurology [Rennes]

Background: Considering that most of semantic dementia (SD) and frontotemporal dementia (FTD) patients show no postmortem Alzheimer's disease (AD) pathology, cerebrospinal fluid (CSF) biomarkers may be of value for distinguishing these patients from those with AD. Additionally, biomarkers may be useful for identifying patients with atypical phenotypic presentations of AD, such as posterior cortical atrophy (PCA) and primary progressive non-fluent or logopenic aphasia (PNFLA). Methods: We investigated CSF biomarkers (beta-amyloid 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau [P-tau]) in 164 patients with AD (n=60), PCA (n=15), behavioral variant FTD (n=27), SD (n=19), (PNFLA) (n=26) and functional cognitive disorders (FCD, n=17). We then examined the diagnostic value of these CSF biomarkers in distinguishing the patients from those with AD. Results: The P-Tau/Aβ42 ratio was found to be the best biomarker for discriminating AD from FTD and SD, with a sensitivity of 91.7% and 98.3%, respectively, and a specificity of 92.6% and 84.2%, respectively. As expected, biomarkers were less effective in differentiating AD from PNFLA and PCA, as significant proportions of PCA and PNFLA patients (60% and 61.5%, respectively) had concurrent alterations of both T-tau/Aβ42 and P-Tau/Aβ42 ratios. None of the FCD patients had a typical AD CSF profile or abnormal T-tau/Aβ42 or P-Tau/Aβ42 ratios. Conclusion: The P-Tau/Aβ42 ratio is a useful tool to discriminate AD from both FTD and SD, which are known to involve pathological processes distinct from AD. Biomarkers could be useful for identifying patients with an atypical AD phenotype that includes PNFLA and PCA.

Mots clés: Alzheimer's disease; Frontotemporal dementia; Semantic dementia; Posterior Cortical Atrophy; Biomarkers

Leonardo Cruz de Souza, Foudil Lamari, Serge Belliard, Claude Jardel, Caroline Houillier, et al.. Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's disease from cortical dementias. Journal of Neurology, Neurosurgery and Psychiatry, 2010, 82 (3), pp.240. ⟨10.1136/jnnp.2010.207183⟩. ⟨hal-00570141⟩