Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's disease from other cortical dementias
Journal of Neurology, Neurosurgery and Psychiatry
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 nonfluent or logopenic aphasia (PNFLA). Methods: We investigated CSF
... markers (beta-amyloid 1-42 (Aβ 42 ), 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/Aβ 42 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/Aβ 42 and P-Tau/Aβ 42 ratios. None of the FCD patients had a typical AD CSF profile or abnormal T-tau/Aβ 42 or P-Tau/Aβ 42 ratios. Conclusion: The P-Tau/Aβ 42 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.