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J Alzheimers Dis. 2015;43(4):1429-40. doi: 10.3233/JAD-141122.

Cerebrospinal fluid biomarkers can play a pivotal role in the diagnostic work up of primary progressive aphasia.

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Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
Department of Neurology, Papa Giovanni XXIII Hospital, Bergamo, Italy.
Laboraf, San Raffaele Scientific Institute, Milan, Italy.



Three variants of primary progressive aphasia (PPA) have been currently characterized: non fluent/agrammatic (nfv-PPA), semantic (sv-PPA), and logopenic variant (lv-PPA). lv-PPA is most commonly associated with Alzheimer's disease (AD), while nfv-PPA and sv-PPA are related to frontotemporal lobar degeneration.


We aimed to determine whether cerebrospinal fluid (CSF) amyloid-β42 (Aβ42), total tau protein (t-tau), and phosphorylated tau (p-tau), frequently abnormal in AD, could constitute a useful tool in the PPA diagnostic work up, in order to identify subjects with an underlying AD pathology.


We measured CSF biomarker levels in a group of twenty-eight patients, fourteen lv-PPA, nine nfv-PPA, and five sv-PPA.


Since there were no significant differences in any of the parameters investigated between nfv-PPA and sv-PPA, the two groups were considered as one (nfv/sv-PPA). At diagnosis, lv-PPA were older than nfv/sv-PPA patients (mean values: 70.7 versus 64.6 years, p = 0.02). CSF biomarker mean concentrations were significantly different in lv-PPA versus nfv/sv-PPA patients (p = 0.000): Aβ42 350.64 versus 661.64 ng/L; tau 631.21 versus 232.71 ng/L; p-tau 101 versus 38.21 ng/L. According to the recent AD diagnostic criteria, (Cummings et al., 2013) eleven lv-PPA and only one nfv/sv-PPA showed a liquoral pattern typical for AD. Finally lv-PPA had CSF biomarker levels very similar to a sample of 72 AD patients from our Department.


Our data showed that CSF biomarkers can easily and reliably detect those patients with language disorders due to an underlying AD pathology, thus offering the possibility of targeted therapeutic interventions. However, because of the small sample size, such analyses should be reproduced in larger populations of patients to confirm our data.


CSF biomarkers; logopenic variant; non fluent-agrammatic variant; primary progressive aphasia; semantic variant

[Indexed for MEDLINE]

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