CSF ferritin in the clinicopathological progression of Alzheimer's disease and associations with APOE and inflammation biomarkers

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CSF ferritin in the clinicopathological progression of Alzheimer's disease and associations with APOE and inflammation biomarkers

Ayton, Scott (författare): University of Melbourne,The Florey Institute of Neuroscience and Mental Health

Janelidze, Shorena (författare): Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups

Kalinowski, Pawel (författare): The Florey Institute of Neuroscience and Mental Health,University of Melbourne

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Palmqvist, Sebastian (författare): Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital

Belaidi, Abdel Ali (författare): University of Melbourne,The Florey Institute of Neuroscience and Mental Health

Stomrud, Erik (författare): Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital

Roberts, Anne (författare): Emory University

Roberts, Blaine (författare): Emory University

Hansson, Oskar (författare): Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups

Bush, Ashley Ian (författare): The Florey Institute of Neuroscience and Mental Health,University of Melbourne

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2022-11-10
2023
Engelska.
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 94:3, s. 211-219

Relaterad länk:: http://dx.doi.org/10...; visa fler...; https://lup.lub.lu.s...; https://doi.org/10.1...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

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Background: A putative role for iron in driving Alzheimer's disease (AD) progression is complicated by previously reported associations with neuroinflammation, apolipoprotein E and AD proteinopathy. To establish how iron interacts with clinicopathological features of AD and at what disease stage iron influences cognitive outcomes, we investigated the association of cerebrospinal fluid (CSF) biomarkers of iron (ferritin), inflammation (acute phase response proteins) and apolipoproteins with pathological biomarkers (CSF Aβ42/t-tau, p-tau181), clinical staging and longitudinal cognitive deterioration in subjects from the BioFINDER cohort, with replication of key results in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Methods: Ferritin, acute phase response proteins (n=9) and apolipoproteins (n=6) were measured in CSF samples from BioFINDER (n=1239; 4 years cognitive follow-up) participants stratified by cognitive status (cognitively unimpaired, mild cognitive impairment, AD) and for the presence of amyloid and tangle pathology using CSF Aβ42/t-tau (A+) and p-tau181 (T+). The ferritin and apolipoprotein E associations were replicated in the ADNI (n=264) cohort. Results: In both cohorts, ferritin and apoE were elevated in A-T+ and A+T+ subjects (16%-40%), but not clinical diagnosis. Other apolipoproteins and acute phase response proteins increased with clinical diagnosis, not pathology. CSF ferritin was positively associated with p-tau181, which was mediated by apolipoprotein E. An optimised threshold of ferritin predicted cognitive deterioration in mild cognitive impairment subjects in the BioFINDER cohort, especially those people classified as A-T- and A+T-. Conclusions: CSF markers of iron and neuroinflammation have distinct associations with disease stages, while iron may be more intimately associated with apolipoprotein E and tau pathology.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

alzheimer's disease
iron deposition

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Av författaren/redakt...: Ayton, Scott; Janelidze, Shore ...; Kalinowski, Pawe ...; Palmqvist, Sebas ...; Belaidi, Abdel A ...; Stomrud, Erik; visa fler...; Roberts, Anne; Roberts, Blaine; Hansson, Oskar; Bush, Ashley Ian; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

Artiklar i publikationen: Journal of Neuro ...

Av lärosätet: Lunds universitet

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