YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration

• Type of Material: Article
• Authors: Yanaika S Hok-A-Hin, VU University Medical Center; Jeroen JM Hoozemans, VU University Medical Center; William Hu, Emory University; Dorine Wouters, VU University Medical Center; Jennifer Howell, Emory University; Alberto Rábano, Alzheimer’s Centre Reina Sofía-CIEN Foundation; Wiesje M van der Flier, VU University Medical Centers; Yolande AL Pijnenburg, VU University Medical Centers; Charlotte E Teunissen, VU University Medical Center; Marta del Campo, VU University Medical Center
• Language: English
• Date: 2022-07-25
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13195-022-01039-y
• Title of Journal or Parent Work: Alzheimers Research & Therapy
• Volume: 14
• Grant/Funding Information: This project was funded by the memorable project PRODIA (project number 733050206) which is supported by ZonMw (The Netherlands).
• Keywords: Chitinase 3-like I; YKL-40; Alzheimer’s disease; Neuroinflammation; Frontotemporal lobar degeneration; Brain

Abstract

Background YKL-40 (Chitinase 3-like I) is increased in CSF of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) patients and is therefore considered a potential neuroinflammatory biomarker. Whether changed YKL-40 levels in the CSF reflect dysregulation of YKL-40 in the brain is not completely understood yet. We aimed to extensively analyze YKL-40 levels in the brain of AD and different FTLD pathological subtypes. The direct relationship between YKL-40 levels in post-mortem brain and ante-mortem CSF was examined in a small set of paired brain-CSF samples. Method YKL-40 was analyzed in post-mortem temporal and frontal cortex of non-demented controls and patients with AD and FTLD (including FTLD-Tau and FTLD-TDP) pathology by immunohistochemistry (temporal cortex: 51 controls and 56 AD and frontal cortex: 7 controls and 24 FTLD patients), western blot (frontal cortex: 14 controls, 5 AD and 67 FTLD patients), or ELISA (temporal cortex: 11 controls and 7 AD and frontal cortex: 14 controls, 5 AD and 67 FTLD patients). YKL-40 levels were also measured in paired post-mortem brain and ante-mortem CSF samples from dementia patients (n = 9, time-interval collection: 1.4 years) by ELISA. Results We observed that YKL-40 post-mortem brain levels were similar between AD, FTLD, and controls as shown by immunohistochemistry, western blot, and ELISA. Interestingly, strong YKL-40 immunoreactivity was observed in AD cases with cerebral amyloid angiopathy (CAA; n = 6). In paired CSF-brain samples, YKL-40 concentration was 8-times higher in CSF compared to brain. Conclusion Our data suggest that CSF YKL-40 changes may not reflect YKL-40 changes within AD and FTLD pathological brain areas. The YKL-40 reactivity associated with classical CAA hallmarks indicates a possible relationship between YKL-40, neuroinflammation, and vascular pathology.