Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's disease from other cortical dementias.
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 (Aβ(42)), 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/Aβ(42) 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/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.


CONCLUSIONS
The P-Tau/Aβ(42) 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.
de Souza
Leonardo Cruz
LC
CRICM, UPMC Univ Paris 06, Pitié-Salpêtrière Hospital, Paris, France.
Lamari
Foudil
F
Belliard
Serge
S
Jardel
Claude
C
Houillier
Caroline
C
De Paz
Raphael
R
Dubois
Bruno
B
Sarazin
Marie
M
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D018888:Aphasia, Primary Progressive / Q000134:cerebrospinal fluid / Q000175:diagnosis; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002540:Cerebral Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins