Localization and protein levels of YKL‐40 in postmortem brain of frontotemporal dementia and Alzheimer's disease cases: Molecular and cell biology/neuroinflammation. (7th December 2020)

• Record Type: Journal Article
• Authors: Hok‐A‐Hin, Yanaika S.; Hu, William T.; Wouters, Dorine; Boonkamp, Lynn; Howell, J. Christina; Rabano, Alberto; Pijnenburg, Yolande A.L.; Teunissen, Charlotte E.; Hoozemans, Jeroen J.M.; Del Campo, Marta
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 2
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.044523
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Levels of the inflammatory protein YKL‐40 (Chitinase 3‐like I) are increased in CSF of patients with Frontotemporal dementia (FTD) and Alzheimer's disease (AD), suggesting YKL‐40 is a potential CSF biomarker reflecting the ongoing neuroinflammatory process. How YKL‐40 is localized and expressed in the brain in various neurodegenerative diseases is still elusive. In this study, we assessed the presence and levels of YKL‐40 in post‐mortem brain tissue of non‐demented controls and dementia cases with different pathologies (FTD and AD). In addition, we addressed the correlation of YKL‐40 levels between post‐mortem tissue and ante‐mortem CSF. Method: The presence of YKL‐40 was analyzed in post‐mortem frontal or temporal cortex of non‐demented controls (NDC, total n = 83), FTD patients (n = 90), and AD patients (n = 59) by immunohistochemistry, western blot or ELISA (see Table 1). In a subset of cases where paired ante‐mortem CSF was available, CSF YKL‐40 was also measured by ELISA (n = 9, time interval CSF and post‐mortem collection: 1, 4 years). Result: YKL‐40 appeared to be mainly detected in astrocytes. YKL‐40 levels were similar between FTD or AD and non‐demented controls by either immunohistochemistry, western blot, or ELISA (p>0.05). No correlation between ante‐mortem CSF YKL‐40 and post‐mortem brain YKL‐40 was observed (r = ‐0.49; p>0.05). Interestingly, strong YKL‐40 immunoreactivity was observed in AD cases with an increased presence of cerebral amyloid angiopathy (CAA). Conclusion: Our data suggest that CSF YKL‐40 changes do not mirror the overall pathological changes affected in FTD or AD. Increased presence of YKL‐40 in AD cases is strongly associated with the presence of CAA and most likely reflects the intense neuroinflammatory response associated with CAA.