YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration
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 b...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-022-01039-y |
| _version_ | 1828778314760716288 |
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| author | Yanaika S. Hok-A-Hin Jeroen J. M. Hoozemans William T. Hu Dorine Wouters Jennifer C. Howell Alberto Rábano Wiesje M. van der Flier Yolande A. L. Pijnenburg Charlotte E. Teunissen Marta del Campo |
| author_facet | Yanaika S. Hok-A-Hin Jeroen J. M. Hoozemans William T. Hu Dorine Wouters Jennifer C. Howell Alberto Rábano Wiesje M. van der Flier Yolande A. L. Pijnenburg Charlotte E. Teunissen Marta del Campo |
| author_sort | Yanaika S. Hok-A-Hin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T16:38:47Z |
| format | Article |
| id | doaj.art-119f87756ba34fef8a830eeee371d12b |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-11T16:38:47Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-119f87756ba34fef8a830eeee371d12b2022-12-22T00:58:22ZengBMCAlzheimer’s Research & Therapy1758-91932022-07-0114111110.1186/s13195-022-01039-yYKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degenerationYanaika S. Hok-A-Hin0Jeroen J. M. Hoozemans1William T. Hu2Dorine Wouters3Jennifer C. Howell4Alberto Rábano5Wiesje M. van der Flier6Yolande A. L. Pijnenburg7Charlotte E. Teunissen8Marta del Campo9Neurochemistry Laboratory, Clinical Chemistry department, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMCDepartment of Pathology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMCDepartment of Neurology, Center for Neurodegenerative Diseases Research, Alzheimer’s Disease Research Center, Emory University School of MedicineNeurochemistry Laboratory, Clinical Chemistry department, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMCDepartment of Neurology, Center for Neurodegenerative Diseases Research, Alzheimer’s Disease Research Center, Emory University School of MedicineCIEN Tissue Bank, Alzheimer’s Centre Reina Sofía-CIEN FoundationAlzheimer Centre Amsterdam, Department of Neurology, Amsterdam Neuroscience, VU University Medical CentersAlzheimer Centre Amsterdam, Department of Neurology, Amsterdam Neuroscience, VU University Medical CentersNeurochemistry Laboratory, Clinical Chemistry department, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMCNeurochemistry Laboratory, Clinical Chemistry department, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMCAbstract 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.https://doi.org/10.1186/s13195-022-01039-yYKL-40Chitinase 3-like IAlzheimer’s diseaseFrontotemporal lobar degenerationNeuroinflammationBrain |
| spellingShingle | Yanaika S. Hok-A-Hin Jeroen J. M. Hoozemans William T. Hu Dorine Wouters Jennifer C. Howell Alberto Rábano Wiesje M. van der Flier Yolande A. L. Pijnenburg Charlotte E. Teunissen Marta del Campo YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration Alzheimer’s Research & Therapy YKL-40 Chitinase 3-like I Alzheimer’s disease Frontotemporal lobar degeneration Neuroinflammation Brain |
| title | YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration |
| title_full | YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration |
| title_fullStr | YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration |
| title_full_unstemmed | YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration |
| title_short | YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration |
| title_sort | ykl 40 changes are not detected in post mortem brain of patients with alzheimer s disease and frontotemporal lobar degeneration |
| topic | YKL-40 Chitinase 3-like I Alzheimer’s disease Frontotemporal lobar degeneration Neuroinflammation Brain |
| url | https://doi.org/10.1186/s13195-022-01039-y |
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