Background: The incoming disease-modifying therapies against Alzheimer's disease (AD) require reliable diagnostic markers to correctly enroll patients all over the world. CSF AD biomarkers, namely amyloid-beta 42 (A beta 42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-taul 81), showed good diagnostic accuracy in detecting AD pathology, but their real usefulness in daily clinical practice is still a matter of debate. Therefore, further validation in complex clinical settings, that is patients with different types of dementia, is needed to uphold their future worldwide adoption.Methods: We measured CSF AD biomarkers' concentrations in a sample of 526 patients with a clinical diagnosis of dementia (277 with AD and 249 with Other Type of Dementia, OTD). Brain FDG-PET was also considered in a subsample of 54 patients with a mismatch between the clinical diagnosis and the CSF findings.Results: A p-tau181/A beta 42 ratio higher than 0.13 showed the best diagnostic performance in differentiating AD from OTD (86% accuracy index, 74% sensitivity, 81% specificity). In cases with a mismatch between clinical diagnosis and CSF findings, brain FUG-PET partially agreed with the p-tau181/A beta 42 ratio, thus determining an increase in CSF accuracy.Conclusion: The p-tau181/A beta 42 ratio alone might reliably detect AD pathology in heterogeneous samples of patients suffering from different types of dementia. It might constitute a simple, cost-effective and reproducible in vivo proxy of AD suitable to be adopted worldwide not only in daily clinical practice but also in future experimental trials, to avoid the enrolment of misdiagnosed AD patients.

The CSF p-tau181/Aβ42 Ratio Offers a Good Accuracy "In Vivo" in the Differential Diagnosis of Alzheimer's Dementia / Santangelo, R.; Dell'Edera, A.; Sala, A.; Cecchetti, G.; Masserini, F.; Caso, F.; Pinto, P.; Leocani, L.; Falautano, M.; Passerini, G.; Martinelli, V.; Comi, G.; Perani, D.; Magnani, G.. - In: CURRENT ALZHEIMER RESEARCH. - ISSN 1567-2050. - 16:7(2019), pp. 587-595. [10.2174/1567205016666190725150836]

The CSF p-tau181/Aβ42 Ratio Offers a Good Accuracy "In Vivo" in the Differential Diagnosis of Alzheimer's Dementia

Leocani L.;Comi G.;Perani D.;
2019-01-01

Abstract

Background: The incoming disease-modifying therapies against Alzheimer's disease (AD) require reliable diagnostic markers to correctly enroll patients all over the world. CSF AD biomarkers, namely amyloid-beta 42 (A beta 42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-taul 81), showed good diagnostic accuracy in detecting AD pathology, but their real usefulness in daily clinical practice is still a matter of debate. Therefore, further validation in complex clinical settings, that is patients with different types of dementia, is needed to uphold their future worldwide adoption.Methods: We measured CSF AD biomarkers' concentrations in a sample of 526 patients with a clinical diagnosis of dementia (277 with AD and 249 with Other Type of Dementia, OTD). Brain FDG-PET was also considered in a subsample of 54 patients with a mismatch between the clinical diagnosis and the CSF findings.Results: A p-tau181/A beta 42 ratio higher than 0.13 showed the best diagnostic performance in differentiating AD from OTD (86% accuracy index, 74% sensitivity, 81% specificity). In cases with a mismatch between clinical diagnosis and CSF findings, brain FUG-PET partially agreed with the p-tau181/A beta 42 ratio, thus determining an increase in CSF accuracy.Conclusion: The p-tau181/A beta 42 ratio alone might reliably detect AD pathology in heterogeneous samples of patients suffering from different types of dementia. It might constitute a simple, cost-effective and reproducible in vivo proxy of AD suitable to be adopted worldwide not only in daily clinical practice but also in future experimental trials, to avoid the enrolment of misdiagnosed AD patients.
2019
Alzheimer's disease; amyloid beta 42; cerebrospinal fluid biomarkers; dementia; diagnostic accuracy; phosphorylated tau.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/94531
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 16
social impact