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Evidence that iron accelerates Alzheimer's pathology: a CSF biomarker study.
J Neurol Neurosurg Psychiatry. 2018 05; 89(5):456-460.JN

Abstract

OBJECTIVE

To investigate whether cerebrospinal fluid (CSF) ferritin (reporting brain iron) is associated with longitudinal changes in CSF β-amyloid (Aβ) and tau.

METHODS

Mixed-effects models of CSF Aβ1-42 and tau were constructed using data from 296 participants who had baseline measurement of CSF ferritin and annual measurement of CSF tau and Aβ1-42 for up to 5 years.

RESULTS

In subjects with biomarker-confirmed Alzheimer's pathology, high CSF ferritin (>6.2 ng/mL) was associated with accelerated depreciation of CSF Aβ1-42 (reporting increased plaque formation; p=0.0001). CSF ferritin was neither associated with changes in CSF tau in the same subjects, nor longitudinal changes in CSF tau or Aβ1-42 in subjects with low baseline pathology. In simulation modelling of the natural history of Aβ deposition, which we estimated to occur over 31.4 years, we predicted that it would take 12.6 years to reach the pathology threshold value of CSF Aβ from healthy normal levels, and this interval is not affected by CSF ferritin. CSF ferritin influences the fall in CSF Aβ over the next phase, where high CSF ferritin accelerated the transition from threshold preclinical Aβ levels to the average level of Alzheimer's subjects from 18.8 to 10.8 years.

CONCLUSIONS

Iron might facilitate Aβ deposition in Alzheimer's and accelerate the disease process.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Ayton S
The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia.
Diouf I
The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia. Health and Biosecurity/Australian E-Health Research Centre, CSIRO, Brisbane, Australia.
Bush AI
The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia. Cooperative Research Center for Mental Health, Victoria, Australia.
Alzheimer’s disease Neuroimaging Initiative
No affiliation info available

MeSH

AgedAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersFemaleFerritinsHumansIronMalePeptide Fragmentstau Proteins

Pub Type(s)

Journal Article
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

28939683

Citation

Ayton, Scott, et al. "Evidence That Iron Accelerates Alzheimer's Pathology: a CSF Biomarker Study." Journal of Neurology, Neurosurgery, and Psychiatry, vol. 89, no. 5, 2018, pp. 456-460.
Ayton S, Diouf I, Bush AI, et al. Evidence that iron accelerates Alzheimer's pathology: a CSF biomarker study. J Neurol Neurosurg Psychiatry. 2018;89(5):456-460.
Ayton, S., Diouf, I., & Bush, A. I. (2018). Evidence that iron accelerates Alzheimer's pathology: a CSF biomarker study. Journal of Neurology, Neurosurgery, and Psychiatry, 89(5), 456-460. https://doi.org/10.1136/jnnp-2017-316551
Ayton S, et al. Evidence That Iron Accelerates Alzheimer's Pathology: a CSF Biomarker Study. J Neurol Neurosurg Psychiatry. 2018;89(5):456-460. PubMed PMID: 28939683.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence that iron accelerates Alzheimer's pathology: a CSF biomarker study. AU - Ayton,Scott, AU - Diouf,Ibrahima, AU - Bush,Ashley Ian, AU - ,, Y1 - 2017/09/22/ PY - 2017/05/29/received PY - 2017/08/14/revised PY - 2017/08/23/accepted PY - 2017/9/25/pubmed PY - 2019/10/8/medline PY - 2017/9/24/entrez KW - alzheimer’s disease KW - amyloid KW - iron deposition SP - 456 EP - 460 JF - Journal of neurology, neurosurgery, and psychiatry JO - J Neurol Neurosurg Psychiatry VL - 89 IS - 5 N2 - OBJECTIVE: To investigate whether cerebrospinal fluid (CSF) ferritin (reporting brain iron) is associated with longitudinal changes in CSF β-amyloid (Aβ) and tau. METHODS: Mixed-effects models of CSF Aβ1-42 and tau were constructed using data from 296 participants who had baseline measurement of CSF ferritin and annual measurement of CSF tau and Aβ1-42 for up to 5 years. RESULTS: In subjects with biomarker-confirmed Alzheimer's pathology, high CSF ferritin (>6.2 ng/mL) was associated with accelerated depreciation of CSF Aβ1-42 (reporting increased plaque formation; p=0.0001). CSF ferritin was neither associated with changes in CSF tau in the same subjects, nor longitudinal changes in CSF tau or Aβ1-42 in subjects with low baseline pathology. In simulation modelling of the natural history of Aβ deposition, which we estimated to occur over 31.4 years, we predicted that it would take 12.6 years to reach the pathology threshold value of CSF Aβ from healthy normal levels, and this interval is not affected by CSF ferritin. CSF ferritin influences the fall in CSF Aβ over the next phase, where high CSF ferritin accelerated the transition from threshold preclinical Aβ levels to the average level of Alzheimer's subjects from 18.8 to 10.8 years. CONCLUSIONS: Iron might facilitate Aβ deposition in Alzheimer's and accelerate the disease process. SN - 1468-330X UR - https://www.unboundmedicine.com/medline/citation/28939683/Evidence_that_iron_accelerates_Alzheimer's_pathology:_a_CSF_biomarker_study_ DB - PRIME DP - Unbound Medicine ER -