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Cerebrospinal fluid ceruloplasmin levels predict cognitive decline and brain atrophy in people with underlying β-amyloid pathology.
Neurobiol Dis. 2020 06; 139:104810.ND

Abstract

OBJECTIVES

The mechanisms leading to neurodegeneration in Alzheimer's disease (AD) may involve oxidative stress and neuroinflammation. Ceruloplasmin (Cp) is a circulating protein that intersects both these pathways, since its expression is increased during the acute phase response, and the protein acts to lower pro-oxidant iron in cells. Since the role of Cp in AD, and its potential for use as a biomarker is not established, we investigated CSF Cp and its association with longitudinal outcome measures related to AD.

METHODS

This was an observational study of 268 people from the Alzheimer's Disease Neuroimaging (ADNI) cohort. Subjects were classified clinically as having AD, mild cognitive impairment (MCI) or were cognitively normal (CN), and were also classified as being positive for β-amyloid using established thresholds in the CSF t-tau/Aβ42 ratio. Subjects underwent cognitive tests and MRI studies every 6 months for 2 years, then yearly thereafter for up to 6 years.

RESULTS

At baseline, CSF Cp was not associated with clinical or pathological diagnosis, but we found an unexpected association between CSF Cp and levels of CSF apolipoprotein E. In longitudinal analysis, high level of CSF Cp was associated with accelerated cognitive decline (as assessed by ADAS-Cog, CDR-SB, and MMSE) and ventricular volume enlargement in people classified as MCI and who had underlying β-amyloid pathology.

CONCLUSION

These results raise new questions into the role of Cp in neuroinflammation, oxidative stress, and APOE pathways involved in AD, and reveal the potential for this protein to be used as a biomarker in disease prognostication.

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Authors+Show Affiliations

Diouf I
Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia; CSIRO Health and Biosecurity/Australian E-Health Research Centre, Brisbane, Australia.
Bush AI
Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia.
Ayton S
Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia. Electronic address: scott.ayton@florey.edu.au.
Alzheimer's disease Neuroimaging Initiative
No affiliation info available

MeSH

AgedAlzheimer DiseaseAmyloid beta-PeptidesApolipoproteins EAtrophyBiomarkersBrainCeruloplasminCognitive DysfunctionDisease ProgressionFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological Teststau Proteins

Pub Type(s)

Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

32087292

Citation

Diouf, Ibrahima, et al. "Cerebrospinal Fluid Ceruloplasmin Levels Predict Cognitive Decline and Brain Atrophy in People With Underlying Β-amyloid Pathology." Neurobiology of Disease, vol. 139, 2020, p. 104810.
Diouf I, Bush AI, Ayton S, et al. Cerebrospinal fluid ceruloplasmin levels predict cognitive decline and brain atrophy in people with underlying β-amyloid pathology. Neurobiol Dis. 2020;139:104810.
Diouf, I., Bush, A. I., & Ayton, S. (2020). Cerebrospinal fluid ceruloplasmin levels predict cognitive decline and brain atrophy in people with underlying β-amyloid pathology. Neurobiology of Disease, 139, 104810. https://doi.org/10.1016/j.nbd.2020.104810
Diouf I, et al. Cerebrospinal Fluid Ceruloplasmin Levels Predict Cognitive Decline and Brain Atrophy in People With Underlying Β-amyloid Pathology. Neurobiol Dis. 2020;139:104810. PubMed PMID: 32087292.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebrospinal fluid ceruloplasmin levels predict cognitive decline and brain atrophy in people with underlying β-amyloid pathology. AU - Diouf,Ibrahima, AU - Bush,Ashley I, AU - Ayton,Scott, AU - ,, Y1 - 2020/02/19/ PY - 2019/08/15/received PY - 2020/02/03/revised PY - 2020/02/18/accepted PY - 2020/2/23/pubmed PY - 2021/4/13/medline PY - 2020/2/23/entrez KW - Alzheimer's disease KW - Biomarkers KW - Ceruloplasmin KW - Inflammation KW - Oxidative stress SP - 104810 EP - 104810 JF - Neurobiology of disease JO - Neurobiol Dis VL - 139 N2 - OBJECTIVES: The mechanisms leading to neurodegeneration in Alzheimer's disease (AD) may involve oxidative stress and neuroinflammation. Ceruloplasmin (Cp) is a circulating protein that intersects both these pathways, since its expression is increased during the acute phase response, and the protein acts to lower pro-oxidant iron in cells. Since the role of Cp in AD, and its potential for use as a biomarker is not established, we investigated CSF Cp and its association with longitudinal outcome measures related to AD. METHODS: This was an observational study of 268 people from the Alzheimer's Disease Neuroimaging (ADNI) cohort. Subjects were classified clinically as having AD, mild cognitive impairment (MCI) or were cognitively normal (CN), and were also classified as being positive for β-amyloid using established thresholds in the CSF t-tau/Aβ42 ratio. Subjects underwent cognitive tests and MRI studies every 6 months for 2 years, then yearly thereafter for up to 6 years. RESULTS: At baseline, CSF Cp was not associated with clinical or pathological diagnosis, but we found an unexpected association between CSF Cp and levels of CSF apolipoprotein E. In longitudinal analysis, high level of CSF Cp was associated with accelerated cognitive decline (as assessed by ADAS-Cog, CDR-SB, and MMSE) and ventricular volume enlargement in people classified as MCI and who had underlying β-amyloid pathology. CONCLUSION: These results raise new questions into the role of Cp in neuroinflammation, oxidative stress, and APOE pathways involved in AD, and reveal the potential for this protein to be used as a biomarker in disease prognostication. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/32087292/Cerebrospinal_fluid_ceruloplasmin_levels_predict_cognitive_decline_and_brain_atrophy_in_people_with_underlying_β_amyloid_pathology_ DB - PRIME DP - Unbound Medicine ER -