Neuroinflammatory Processes, A1 Astrocyte Activation and Protein Aggregation in the Retina of Alzheimer's Disease Patients, Possible Biomarkers for Early Diagnosis
Neuroinflammatory Processes, A1 Astrocyte Activation and Protein Aggregation in the Retina of Alzheimer's Disease Patients, Possible Biomarkers for Early Diagnosis
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DOI：
10.3389/fnins.2019.00925
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发表时间：
2019-09-04
影响因子：
4.3
通讯作者：
Di Angelantonio, Silvia
中科院分区：
文献类型：
--
作者：
Grimaldi, Alfonso;Pediconi, Natalia;Di Angelantonio, Silvia
阿尔茨海默病（AD）是老年人群中痴呆症的主要原因，其特征是细胞外淀粉样蛋白- β肽聚集，细胞内过度磷酸化的tau沉积，大脑神经变性和神经胶质活化。人们普遍认为缺乏早期诊断标准是导致药物治疗和临床试验失败的主要原因之一；因此，真正的挑战是定义新的生物标志物和非侵入性技术来测量症状前阶段的体内神经病理变化。最近从人类样本和小鼠模型中获得的证据表明，可以检测视网膜中的蛋白质聚集物和其他病理特征，为无创快速检测AD生物标志物铺平了道路。在这里，我们根据疾病相关的小胶质细胞表型（DAM）报告了淀粉样蛋白斑块、tau缠结、神经变性和有害星形胶质细胞和小胶质细胞激活的存在。因此，我们建议人类视网膜作为检测与阿尔茨海默病相关的细胞和分子变化的有用部位。
Alzheimer's disease (AD), a primary cause of dementia in the aging population, is characterized by extracellular amyloid-beta peptides aggregation, intracellular deposits of hyperphosphorylated tau, neurodegeneration and glial activation in the brain. It is commonly thought that the lack of early diagnostic criteria is among the main causes of pharmacological therapy and clinical trials failure; therefore, the actual challenge is to define new biomarkers and non-invasive technologies to measure neuropathological changes in vivo at pre-symptomatic stages. Recent evidences obtained from human samples and mouse models indicate the possibility to detect protein aggregates and other pathological features in the retina, paving the road for non-invasive rapid detection of AD biomarkers. Here, we report the presence of amyloid beta plaques, tau tangles, neurodegeneration and detrimental astrocyte and microglia activation according to a disease associated microglia phenotype (DAM). Thus, we propose the human retina as a useful site for the detection of cellular and molecular changes associated with Alzheimer's disease.