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Cerebrospinal Fluid...
Cerebrospinal Fluid YKL-40 and Chitotriosidase Levels in Frontotemporal Dementia Vary by Clinical, Genetic and Pathological Subtype
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Woollacott, I. O. C. (författare)
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Nicholas, J. M. (författare)
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Heller, C. (författare)
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visa fler...
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Foiani, M. S. (författare)
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Moore, K. M. (författare)
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Russell, L. L. (författare)
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Paterson, R. W. (författare)
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Keshavan, A. (författare)
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Schott, J. M. (författare)
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Warren, J. D. (författare)
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Heslegrave, A. (författare)
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- Zetterberg, Henrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Rohrer, J. D. (författare)
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(creator_code:org_t)
- 2020-04-28
- 2020
- Engelska.
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 49:1, s. 56-76
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https://www.karger.c...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 inGRN(n= 3),MAPT(n= 4), orC9orf72(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 beta-amyloid 1-42 (A beta 42), 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.GRNmutation carriers had higher levels of both proteins than controls andC9orf72expansion carriers, and YKL-40 was higher inMAPTmutation 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 A beta 42, 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 toGRNmutations, while YKL-40 is increased in individuals withMAPTmutations. As glia-derived protein levels generally correlate with T-tau and P-tau levels, they may reflect the glial response to neurodegeneration in FTLD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Geriatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Geriatrics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Astrocytes
- Biomarkers
- Cerebrospinal fluid
- Chitotriosidase
- Frontotemporal dementia
- Microglia
- Neuroinflammation
- Progranulin
- YKL-40
- primary progressive aphasia
- fibrillary acidic protein
- alzheimers-disease
- lobar degeneration
- microglial activation
- potential
- biomarker
- csf
- tau
- inflammation
- macrophage
- Geriatrics & Gerontology
- Neurosciences & Neurology
- Psychiatry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Woollacott, I. O ...
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Nicholas, J. M.
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Heller, C.
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Foiani, M. S.
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Moore, K. M.
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Russell, L. L.
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visa fler...
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Paterson, R. W.
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Keshavan, A.
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Schott, J. M.
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Warren, J. D.
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Heslegrave, A.
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Zetterberg, Henr ...
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Rohrer, J. D.
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Geriatrik
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Psykiatri
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- MEDICIN OCH HÄLSOVETENSKAP
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Dementia and Ger ...
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Göteborgs universitet