Cerebrospinal Fluid Level of YKL-40 Protein in Preclinical and Prodromal Alzheimer's Disease

Antonell, Anna; Mansilla, Alicia; Rami, Lorena; Lladó, Albert; Iranzo, Álex; Olives, Jaume; Balasa, Mircea; Sánchez‐Valle, Raquel; Molinuevo, José Luís

doi:10.3233/jad-140624

Cited by 109 publications

(107 citation statements)

References 26 publications

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“…In agreement with previous studies, CSF YKL40 was increased in FTLD and AD compared to controls 35, 36, 37. FTLD‐TDP had the highest YKL‐40 values, which were comparable to those observed in AD patients, but different to those observed in CON, FTLD‐Tau, or DLB.…”

Section: Discussionsupporting

confidence: 91%

Novel CSF biomarkers to discriminate FTLD and its pathological subtypes

Campo

Galimberti

Elias

et al. 2018

Ann Clin Transl Neurol

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ObjectiveFrontotemporal lobar degeneration (FTLD) is the second most prevalent dementia in young patients and is characterized by the presence of two main protein aggregates in the brain, tau (FTLD‐Tau) or TDP43 (FTLD‐TDP), which likely require distinct pharmacological therapy. However, specific diagnosis of FTLD and its subtypes remains challenging due to largely overlapping clinical phenotypes. Here, we aimed to assess the clinical performance of novel cerebrospinal fluid (CSF) biomarkers for discrimination of FTLD and its pathological subtypes.Methods YKL40, FABP4, MFG‐E8, and the activities of catalase and specific lysosomal enzymes were analyzed in patients with FTLD‐TDP (n = 30), FTLD‐Tau (n = 20), AD (n = 30), DLB (n = 29), and nondemented controls (n = 29) obtained from two different centers. Models were validated in an independent CSF cohort (n = 188).Results YKL40 and catalase activity were increased in FTLD‐TDP cases compared to controls. YKL40 levels were also higher in FTLD‐TDP compared to FTLD‐Tau. We identified biomarker models able to discriminate FTLD from nondemented controls (MFG‐E8, tTau, and Aβ 42; 78% sensitivity and 83% specificity) and non‐FTLD dementia (YKL40, pTau, p/tTau ratio, and age; 90% sensitivity, 78% specificity), which were validated in an independent cohort. In addition, we identified a biomarker model differentiating FTLD‐TDP from FTLD‐Tau (YKL40, MFGE‐8, βHexA together with βHexA/tHex and p/tTau ratios and age) with 80% sensitivity and 82% specificity.InterpretationThis study identifies CSF protein signatures distinguishing FTLD and the two main pathological subtypes with optimal accuracy (specificity/sensitivity > 80%). Validation of these models may allow appropriate selection of cases for clinical trials targeting the accumulation of Tau or TDP43, thereby increasing their efficiency and facilitating the development of successful therapies.

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Section: Discussionsupporting

confidence: 91%

Novel CSF biomarkers to discriminate FTLD and its pathological subtypes

Campo

Galimberti

Elias

et al. 2018

Ann Clin Transl Neurol

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show abstract

“…The CSF YKL-40/Ab42 ratio also predicted the risk of developing cognitive impairment. Further studies validated the presence of elevated YKL-40 levels in the CSF at preclinical stages of AD and their association with disease progression (Antonell et al, 2014;Kester et al, 2015). Moreover, YKL-40 levels are increased in SD but not in PD and DLB thus increasing the specificity of YKL-40 as a biomarker of AD (Wennstrom et al, 2015).…”

Section: Proteinsmentioning

confidence: 92%

CSF biomarkers in neurodegenerative and vascular dementias

Llorens

Schmitz

Ferrer

et al. 2016

Progress in Neurobiology

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“…Par ailleurs, l'acquisition des données est essentiellement faite de manière transversale. Or, les mécanismes biologiques impliqués dans une pathologie du système nerveux central peuvent varier au cours du temps, dans l'espace anatomique, souvent de manière non linéaire [11]. Il sera donc dans l'avenir indispensable de prendre en compte ces dimensions temporelles et spatiales d'évolution des processus pathologiques.…”

Section: Big Dataunclassified