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Mol Psychiatry. 2019 Feb 18. doi: 10.1038/s41380-019-0375-7. [Epub ahead of print]

Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology.

Author information

1
Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Vic, Australia.
2
Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA.
3
CSIRO Health and Biosecurity, Australian E-Health Research Centre, Brisbane, QLD, Australia.
4
Rush Alzheimer Disease Center, Rush University Medical Center, Chicago, IL, USA.
5
University of Missouri Research Reactor, Brockman, Columbia, NY, USA.
6
Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA. martha_morris@rush.edu.
7
Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Vic, Australia. ashley.bush@florey.edu.au.

Abstract

Cortical iron has been shown to be elevated in Alzheimer's disease (AD), but the impact of the directly measured iron on the clinical syndrome has not been assessed. We investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD, its severity, and the rate of cognitive decline in the 12 years prior to death in subjects from the Memory and Aging Project (n = 209). Iron was elevated (β [SE] = 9.7 [2.6]; P = 3.0 × 10-4) in the inferior temporal cortex only in subjects who were diagnosed with clinical AD during life and had a diagnosis of AD confirmed post-mortem by standardized criteria. Although iron was weakly associated with the extent of proteinopathy in tissue with AD neuropathology, it was strongly associated with the rate of cognitive decline (e.g., global cognition: β [SE] = -0.040 [0.005], P = 1.6 × 10-14). Thus, cortical iron might act to propel cognitive deterioration upon the underlying proteinopathy of AD, possibly by inducing oxidative stress or ferroptotic cell death, or may be related to an inflammatory response.

PMID:
30778133
DOI:
10.1038/s41380-019-0375-7

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