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Localization and protein levels of YKL‐40 in postmortem brain of frontotemporal dementia and Alzheimer’s disease cases
Author(s) -
HokAHin 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
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044523
Subject(s) - frontotemporal dementia , dementia , pathology , immunohistochemistry , medicine , western blot , biomarker , alzheimer's disease , frontotemporal lobar degeneration , disease , biology , biochemistry , gene
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.