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- W2896541742 abstract "Alzheimer's disease (AD) proteinopathy is present in ∼30% of cognitively normal elders and is associated with increased risk of dementia. The large variance in rates of decline indicates that other lesions contribute to AD-syndromic progression. We have previously reported, using indirect measures of brain iron-- ferritin in CSF (Ayton et al Nature Communications, 2015, Ayton et al JAMA Neurology, 2017), and by Quantitative Susceptibility Mapping-MRI (Ayton et al Brain, 2017)-- that elevated brain iron predicts cognitive decline across the AD clinical severity spectrum. No previous study has related directly measured brain iron levels to cognitive decline in humans. We investigated the association between post-mortem iron levels in the inferior temporal cortex with clinical and pathological diagnoses of AD, its pathology severity, and annual rate of cognitive decline in the 12 years prior to death of individuals who, at the time of enrolment in the Memory and Aging Project (MAP; n=209), did not have dementia. Iron was elevated (∼20%, P=3.0x10−4) in the inferior temporal cortex specifically in subjects who had both a clinical and pathologic diagnosis of AD. Iron was not elevated in subjects without a clinical diagnosis of AD even in the presence of high AD pathologic burden, suggesting that iron was not merely an epiphenomenon of pathology. Accordingly, in subjects with a pathologic diagnosis of AD, iron in the inferior temporal cortex was weakly associated with the extent of the proteinopathy, but was strongly associated with the rate of decline in cognitive abilities (e.g. Global Cognition; β[S.E.]=-0.040 [0.005], P=1.58x10−14). The influence of iron was greater than that of other AD clinical variables such as neurofibrillary tangles (β[S.E.]=-0.034 [0.006]; P=1.06x10−7) and neuritic plaque (β[S.E.]=-0.003 [0.006]; P=0.351). There is a growing appreciation of the mixed-pathology burden in AD. While iron pathology in AD has been known for some time, there is a poor understanding on the quantitative impact of this lesion to AD progression. These findings highlight the importance of iron in AD, and support lowering iron as a therapeutic strategy, which we are currently investigating in a phase II study of the iron chelator, deferiprone." @default.
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- W2896541742 date "2018-07-01" @default.
- W2896541742 modified "2023-10-16" @default.
- W2896541742 title "P2‐473: BRAIN IRON IS A CO‐PATHOLOGY THAT IS STRONGLY ASSOCIATED WITH COGNITIVE DECLINE IN PEOPLE WITH ALZHEIMER'S PATHOLOGY" @default.
- W2896541742 doi "https://doi.org/10.1016/j.jalz.2018.06.1166" @default.
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