Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's disease from other cortical dementias
- Leonardo Cruz de Souza1,2,
- Foudil Lamari3,
- Serge Belliard4,
- Claude Jardel3,
- Caroline Houillier2,
- Raphael De Paz2,
- Bruno Dubois1,2,
- Marie Sarazin1,2
- 1CRICM, UPMC Univ Paris 06, Pitié-Salpêtrière Hospital, Paris, France
- 2Alzheimer Institute, Research and Resource Memory Centre, Centre de Référence de Démences Rares, Pitié-Salpêtrière Hospital, France
- 3Department of Metabolic Biochemistry, Pitié-Salpêtrière Hospital, Paris, France
- 4Department of Neurology, Centre Hospitalier Régional et Universitaire de Rennes, Rennes, France
- Correspondence to Dr Marie Sarazin, Fédération des maladies du Système Nerveux, Research and Resource Memory Centre, Pavillon Paul Castaigne, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France;
Contributors Statistical analyses were conducted by FL and LCdS.
- Received 27 January 2010
- Revised 26 May 2010
- Accepted 9 June 2010
- Published Online First 27 August 2010
Background Considering that most semantic dementia (SD) and frontotemporal dementia (FTD) patients show no post-mortem 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 The authors 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), behavioural variant FTD (n=27), SD (n=19), PNFLA (n=26) and functional cognitive disorders (FCD, n=17). The authors then examined the diagnostic value of these CSF biomarkers in distinguishing these patients from those with AD.
Results The P-Tau/Aβ42 ratio was found to be the best biomarker for distinguishing 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 distinguish 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.
- Alzheimer's disease
- frontotemporal dementia
- semantic dementia
- posterior cortical atrophy
LCdS and FL contributed equally.
Funding LCdS is supported by a grant from ‘Association France Alzheimer.’
Competing interests During the last 2 years, SB has collaborated with the following pharmaceutical companies: EISAI and Lundbeck. During the last 2 years, BD has collaborated with the following pharmaceutical companies: Eisai, Novartis, Roche, Bristol-Mayer-Squib, Servier. During the last 2 years, MS has collaborated with the following pharmaceutical companies: EISAI and Novartis.
Provenance and peer review Not commissioned; externally peer reviewed.