Biomarkers

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ResearchersAgainstAlzheimer's would like to thank Roche Diagnostics for their support of this project.
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Ferritin

Method of Measurement (Pre-analytical Tools)
Imaging
CSF
Biomarker Measured
Brain iron levels
Use
Monitoring
Susceptibility/risk
Stage of Development
Clinical trials
Active vs Completed Trials
Completed
Aim/Results

Baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer’s risk allele, APOE-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD. Furthermore, using MRI imaging of iron levels, the degree of altered iron accumulations was correlated to the amount of amyloid-β plaques and tau pathology and AD and normal aging show different iron and myelin distribution in frontal cortex. These changes appear to occur after the development of the AD pathological hallmarks, so this may be one way to monitor the progress of the disease.

What is Required from Patients

MRI scan (can induce claustrophobia), invasive lumbar puncture, discomfort, recovery time in clinic to decrease risk of spinal fluid leakage

What is Required from the Health System

MRI machine, MRI technician, physician who can preform a lumbar puncture as well as a clinic designed for this testing, equipped lab (e.g., centrifuge), a way to measure the peptide (e.g., mass spectrometer, protein assay kit, ELISA, or western blot)

Sponsor

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; Cooperative Research Center for Mental Health, Victoria, Australia; Leiden University Medical Centre, Leiden, The Netherlands; Percuros BV, Leiden, The Netherlands

  1. Ayton, S., Faux, N. G., Bush, A. I., Weiner, M. W., Aisen, P., Petersen, R., ... & Beckett, L. (2015). Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE. Nature communications, 6, 6760. https://www.ncbi.nlm.nih.gov/pubmed/25988319

  2. Ayton, S., Diouf, I., & Bush, A. I. (2018). Evidence that iron accelerates Alzheimer’s pathology: a CSF biomarker study. J Neurol Neurosurg Psychiatry, 89(5), 456-460. https://www.ncbi.nlm.nih.gov/pubmed/28939683

  3. “Brain Iron May Predict Progression in Alzheimer's.” https://www.medscape.com/viewarticle/874539

  4. van Duijn, S., Bulk, M., van Duinen, S. G., Nabuurs, R. J., van Buchem, M. A., van der Weerd, L., & Natté, R. (2017). Cortical iron reflects severity of Alzheimer’s disease. Journal of Alzheimer's Disease, 60(4), 1533-1545. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676973/