Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology
Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology
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DOI：
10.1038/s41380-019-0375-7
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发表时间：
2020-11-01
影响因子：
11
通讯作者：
Bush, Ashley I.
中科院分区：
文献类型：
--
作者：
Ayton, Scott;Wang, Yamin;Bush, Ashley I.
已显示皮质铁在阿尔茨海默病（AD）中升高，但尚未评估直接测量的铁对临床综合征的影响。我们研究了死后铁水平与AD的临床和病理诊断、严重程度以及记忆和衰老项目（n=209）受试者死亡前12年内认知能力下降率之间的相关性。只有在生前被诊断为临床AD并在死后通过标准化标准确诊为AD的受试者中，下颞叶皮质铁水平升高（β [SE]=9.7 [2.6]; P=3.0x10（-4））。虽然铁与AD神经病理学组织中蛋白质病变的程度弱相关，但它与认知能力下降的速度强相关（例如，整体认知：β [SE]=-0.040 [0.005]，P=1.6x10（-14））。因此，皮质铁可能通过诱导氧化应激或铁凋亡细胞死亡，或可能与炎症反应有关，从而在AD的基础蛋白质病中推动认知恶化。
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 (beta [SE]=9.7 [2.6]; P=3.0x10(-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: beta [SE]=-0.040 [0.005], P=1.6x10(-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.