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Longitudinal cerebr...
Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer's disease.
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Nordengen, Kaja (författare)
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Kirsebom, Bjørn-Eivind (författare)
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Richter, Grit (författare)
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visa fler...
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Pålhaugen, Lene (författare)
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Gísladóttir, Berglind (författare)
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Siafarikas, Nikias (författare)
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Nakling, Arne (författare)
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Rongve, Arvid (författare)
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Bråthen, Geir (författare)
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Grøntvedt, Gøril Rolfseng (författare)
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Gonzalez-Ortiz, Fernando (författare)
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Waterloo, Knut (författare)
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Sharma, Kulbhushan (författare)
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- Karikari, Thomas (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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Vromen, Eleonora M (författare)
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Tijms, Betty M (författare)
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Visser, Pieter J (författare)
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Selnes, Per (författare)
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Kramberger, Milicia G (författare)
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- Winblad, Bengt (författare)
- Karolinska Institutet
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- Blennow, Kaj, 1958 (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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Fladby, Tormod (författare)
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visa färre...
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Journal of neuroinflammation. - 1742-2094. ; 20:1
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Brain innate immune activation is associated with Alzheimer's disease (AD), but degrees of activation may vary between disease stages. Thus, brain innate immune activation must be assessed in longitudinal clinical studies that include biomarker negative healthy controls and cases with established AD pathology. Here, we employ longitudinally sampled cerebrospinal fluid (CSF) core AD, immune activation and glial biomarkers to investigate early (predementia stage) innate immune activation levels and biomarker profiles.We included non-demented cases from a longitudinal observational cohort study, with CSF samples available at baseline (n=535) and follow-up (n=213), between 1 and 6years from baseline (mean 2.8years). We measured Aβ42/40 ratio, p-tau181, and total-tau to determine Ab (A+), tau-tangle pathology (T+), and neurodegeneration (N+), respectively. We classified individuals into these groups: A-/T-/N-, A+/T-/N-, A+/T+ or N+, or A-/T+ or N+. Using linear and mixed linear regression, we compared levels of CSF sTREM2, YKL-40, clusterin, fractalkine, MCP-1, IL-6, IL-1, IL-18, and IFN-γ both cross-sectionally and longitudinally between groups. A post hoc analysis was also performed to assess biomarker differences between cognitively healthy and impaired individuals in the A+/T+ or N+ group.Cross-sectionally, CSF sTREM2, YKL-40, clusterin and fractalkine were higher only in groups with tau pathology, independent of amyloidosis (p<0.001, A+/T+ or N+ and A-/T+ or N+, compared to A-/T-/N-). No significant group differences were observed for the cytokines CSF MCP-1, IL-6, IL-10, IL18 or IFN-γ. Longitudinally, CSF YKL-40, fractalkine and IFN-γ were all significantly lower in stable A+/T-/N- cases (all p<0.05). CSF sTREM2, YKL-40, clusterin, fractalkine (p<0.001) and MCP-1 (p<0.05) were all higher in T or N+, with or without amyloidosis at baseline, but remained stable over time. High CSF sTREM2 was associated with preserved cognitive function within the A+/T+ or N+ group, relative to the cognitively impaired with the same A/T/N biomarker profile (p<0.01).Immune hypoactivation and reduced neuron-microglia communication are observed in isolated amyloidosis while activation and increased fractalkine accompanies tau pathology in predementia AD. Glial hypo- and hyperactivation through the predementia AD continuum suggests altered glial interaction with Ab and tau pathology, and may necessitate differential treatments, depending on the stage and patient-specific activation patterns.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Humans
- Alzheimer Disease
- pathology
- Chitinase-3-Like Protein 1
- Chemokine CX3CL1
- Clusterin
- Amyloid beta-Peptides
- cerebrospinal fluid
- Interleukin-6
- Amyloidosis
- Biomarkers
- cerebrospinal fluid
- tau Proteins
- cerebrospinal fluid
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Nordengen, Kaja
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Kirsebom, Bjørn- ...
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Richter, Grit
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Pålhaugen, Lene
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Gísladóttir, Ber ...
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Siafarikas, Niki ...
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visa fler...
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Nakling, Arne
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Rongve, Arvid
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Bråthen, Geir
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Grøntvedt, Gøril ...
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Gonzalez-Ortiz, ...
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Waterloo, Knut
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Sharma, Kulbhush ...
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Karikari, Thomas
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Vromen, Eleonora ...
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Tijms, Betty M
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Visser, Pieter J
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Selnes, Per
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Kramberger, Mili ...
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Winblad, Bengt
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Blennow, Kaj, 19 ...
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Fladby, Tormod
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Journal of neuro ...
- Av lärosätet
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Göteborgs universitet
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Karolinska Institutet