Cerebrospinal Fluid YKL-40 and Chitotriosidase Levels in Frontotemporal Dementia Vary by Clinical, Genetic and Pathological Subtype
© 2020 The Author(s) Published by S. Karger AG, Basel..
BACKGROUND: Chronic glial dysfunction may contribute to the pathogenesis of frontotemporal dementia (FTD). Cerebrospinal fluid (CSF) levels of glia-derived proteins YKL-40 and chitotriosidase are increased in Alzheimer's disease (AD) but have not been explored in detail across the spectrum of FTD.
METHODS: We investigated whether CSF YKL-40 and chitotriosidase levels differed between FTD patients and controls, across different clinical and genetic subtypes of FTD, and between individuals with a clinical FTD syndrome due to AD versus non-AD (frontotemporal lobar degeneration, FTLD) pathology (based on CSF neurodegenerative biomarkers). Eighteen healthy controls and 64 people with FTD (behavioural variant FTD, n = 20; primary progressive aphasia [PPA], n = 44: nfvPPA, n = 16, svPPA, n = 11, lvPPA, n = 14, PPA-NOS, n = 3) were included. 10/64 had familial FTD, with mutations in GRN(n = 3), MAPT(n = 4), or C9orf72 (n = 3). 15/64 had neurodegenerative biomarkers consistent with AD pathology. Levels were measured by immunoassay and compared using multiple linear regressions. We also examined relationships of YKL-40 and chitotriosidase with CSF total tau (T-tau), phosphorylated tau 181 (P-tau) and β-amyloid 1-42 (Aβ42), with each other, and with age and disease du-ration.
RESULTS: CSF YKL-40 and chitotriosidase levels were higher in FTD, particularly lvPPA (both) and nfvPPA (YKL-40), compared with controls. GRN mutation carriers had higher levels of both proteins than controls and C9orf72 expansion carriers, and YKL-40 was higher in MAPT mutation carriers than controls. Individuals with underlying AD pathology had higher YKL-40 and chitotriosidase levels than both controls and those with likely FTLD pathology. CSF YKL-40 and chitotriosidase levels were variably associated with levels of T-tau, P-tau and Aβ42, and with each other, depending on clinical syndrome and underlying pathology. CSF YKL-40 but not chitotriosidase was associated with age, but not disease duration.
CONCLUSION: CSF YKL-40 and chitotriosidase levels are increased in individuals with clinical FTD syndromes, particularly due to AD pathology. In a preliminary analysis of genetic groups, levels of both proteins are found to be highly elevated in FTD due to GRN mutations, while YKL-40 is increased in individuals with MAPT mutations. As glia-derived protein levels generally correlate with T-tau and P-tau levels, they may reflect the glial response to neurodegeneration in FTLD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:49 |
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| Enthalten in: |
Dementia and geriatric cognitive disorders - 49(2020), 1 vom: 14., Seite 56-76 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Woollacott, Ione O C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.01.2021 Date Revised 25.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1159/000506282 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM309283469 |
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| 041 | |a eng | ||
| 100 | 1 | |a Woollacott, Ione O C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cerebrospinal Fluid YKL-40 and Chitotriosidase Levels in Frontotemporal Dementia Vary by Clinical, Genetic and Pathological Subtype |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.01.2021 | ||
| 500 | |a Date Revised 25.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Author(s) Published by S. Karger AG, Basel. | ||
| 520 | |a BACKGROUND: Chronic glial dysfunction may contribute to the pathogenesis of frontotemporal dementia (FTD). Cerebrospinal fluid (CSF) levels of glia-derived proteins YKL-40 and chitotriosidase are increased in Alzheimer's disease (AD) but have not been explored in detail across the spectrum of FTD | ||
| 520 | |a METHODS: We investigated whether CSF YKL-40 and chitotriosidase levels differed between FTD patients and controls, across different clinical and genetic subtypes of FTD, and between individuals with a clinical FTD syndrome due to AD versus non-AD (frontotemporal lobar degeneration, FTLD) pathology (based on CSF neurodegenerative biomarkers). Eighteen healthy controls and 64 people with FTD (behavioural variant FTD, n = 20; primary progressive aphasia [PPA], n = 44: nfvPPA, n = 16, svPPA, n = 11, lvPPA, n = 14, PPA-NOS, n = 3) were included. 10/64 had familial FTD, with mutations in GRN(n = 3), MAPT(n = 4), or C9orf72 (n = 3). 15/64 had neurodegenerative biomarkers consistent with AD pathology. Levels were measured by immunoassay and compared using multiple linear regressions. We also examined relationships of YKL-40 and chitotriosidase with CSF total tau (T-tau), phosphorylated tau 181 (P-tau) and β-amyloid 1-42 (Aβ42), with each other, and with age and disease du-ration | ||
| 520 | |a RESULTS: CSF YKL-40 and chitotriosidase levels were higher in FTD, particularly lvPPA (both) and nfvPPA (YKL-40), compared with controls. GRN mutation carriers had higher levels of both proteins than controls and C9orf72 expansion carriers, and YKL-40 was higher in MAPT mutation carriers than controls. Individuals with underlying AD pathology had higher YKL-40 and chitotriosidase levels than both controls and those with likely FTLD pathology. CSF YKL-40 and chitotriosidase levels were variably associated with levels of T-tau, P-tau and Aβ42, and with each other, depending on clinical syndrome and underlying pathology. CSF YKL-40 but not chitotriosidase was associated with age, but not disease duration | ||
| 520 | |a CONCLUSION: CSF YKL-40 and chitotriosidase levels are increased in individuals with clinical FTD syndromes, particularly due to AD pathology. In a preliminary analysis of genetic groups, levels of both proteins are found to be highly elevated in FTD due to GRN mutations, while YKL-40 is increased in individuals with MAPT mutations. As glia-derived protein levels generally correlate with T-tau and P-tau levels, they may reflect the glial response to neurodegeneration in FTLD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Astrocytes | |
| 650 | 4 | |a Biomarkers | |
| 650 | 4 | |a CHI3L1 | |
| 650 | 4 | |a Cerebrospinal fluid | |
| 650 | 4 | |a Chitotriosidase | |
| 650 | 4 | |a Frontotemporal dementia | |
| 650 | 4 | |a Microglia | |
| 650 | 4 | |a Neuroinflammation | |
| 650 | 4 | |a Progranulin | |
| 650 | 4 | |a YKL-40 | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a C9orf72 Protein |2 NLM | |
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| 650 | 7 | |a MAPT protein, human |2 NLM | |
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| 650 | 7 | |a tau Proteins |2 NLM | |
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| 700 | 1 | |a Nicholas, Jennifer M |e verfasserin |4 aut | |
| 700 | 1 | |a Heller, Carolin |e verfasserin |4 aut | |
| 700 | 1 | |a Foiani, Martha S |e verfasserin |4 aut | |
| 700 | 1 | |a Moore, Katrina M |e verfasserin |4 aut | |
| 700 | 1 | |a Russell, Lucy L |e verfasserin |4 aut | |
| 700 | 1 | |a Paterson, Ross W |e verfasserin |4 aut | |
| 700 | 1 | |a Keshavan, Ashvini |e verfasserin |4 aut | |
| 700 | 1 | |a Schott, Jonathan M |e verfasserin |4 aut | |
| 700 | 1 | |a Warren, Jason D |e verfasserin |4 aut | |
| 700 | 1 | |a Heslegrave, Amanda |e verfasserin |4 aut | |
| 700 | 1 | |a Zetterberg, Henrik |e verfasserin |4 aut | |
| 700 | 1 | |a Rohrer, Jonathan D |e verfasserin |4 aut | |
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