Alzheimer’s disease contributes to 60–70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer’s disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aβ pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.

Graphical Abstract

中文翻译：

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BIN1 致力于推翻阿尔茨海默病的统治：对淀粉样蛋白和 Tau 神经病理学的影响

阿尔茨海默病占普通人群所有痴呆症病例的 60-70%。桥接整合子 (BIN1) 属于 BIN1/amphiphyn/RVS167 (BAR) 超家族，已被确定会影响阿尔茨海默病 (AD) 的两个主要病理标志，即 β 淀粉样蛋白 (Aβ) 和 tau 蛋白积累。发现迟发性 AD 皮质神经元中 BIN1 敲低会增加 Aβ 积累，这是由于 BACE1 在扩大的早期内涵体中积累所致。两个 BIN1 突变体 KR 和 PL 被鉴定出表现出 Aβ 积累。此外，BIN1 相关多态性导致的 BIN1 缺陷会损害与 tau 的相互作用，从而提高 tau 磷酸化，改变突触结构和 tau 功能。尽管 BIN1 在神经元组织中的确切作用需要进一步研究，但作者的目标是揭示 BIN1 的潜力并揭示其对 tau 和 Aβ 病理学的影响，以帮助全球的 AD 研究人员检查 BIN1，作为适当的选择。疾病管理的靶基因。

图形概要