Objective Alzheimer disease (AD) is the leading cause of dementia, and although its etiology remains unclear, it seems that type 2 diabetes mellitus (T2DM) and other prediabetic states of insulin resistance could contribute to the appearance of sporadic AD. As such, we have assessed whether tau and β-amyloid (Aβ) deposits might be present in pancreatic tissue of subjects with AD, and whether amylin, an amyloidogenic protein deposited in the pancreas of T2DM patients, might accumulate in the brain of AD patients. Methods We studied pancreatic and brain tissue from 48 individuals with no neuropathological alterations and from 87 subjects diagnosed with AD. We examined Aβ and tau accumulation in the pancreas as well as that of amylin in the brain. Moreover, we performed proximity ligation assays to ascertain whether tau and/or Aβ interact with amylin in either the pancreas or brain of these subjects. Results Cytoplasmic tau and Aβ protein deposits were detected in pancreatic β cells of subjects with AD as well as in subjects with a normal neuropathological examination but with a history of T2DM and in a small cohort of control subjects without T2DM. Furthermore, we found amylin deposits in the brain of these subjects, providing histological evidence that amylin can interact with Aβ and tau in both the pancreas and hippocampus. Interpretation The presence of both tau and Aβ inclusions in pancreatic β cells, and of amylin deposits in the brain, provides new evidence of a potential overlap in the mechanisms underlying the pathogenesis of T2DM and AD. ANN NEUROL 2019;86:539-551.

中文翻译：

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胰淀素作为 2 型糖尿病和阿尔茨海默病之间的潜在联系

目的阿尔茨海默病 (AD) 是痴呆的主要原因，尽管其病因尚不清楚，但似乎 2 型糖尿病 (T2DM) 和其他胰岛素抵抗的糖尿病前期状态可能导致散发性 AD 的出现。因此，我们评估了 AD 患者的胰腺组织中是否存在 tau 和 β-淀粉样蛋白 (Aβ) 沉积物，以及胰淀素（一种沉积在 T2DM 患者胰腺中的淀粉样蛋白）是否可能在 AD 患者的大脑中积聚. 方法 我们研究了 48 名没有神经病理学改变的个体和 87 名诊断为 AD 的受试者的胰腺和脑组织。我们检查了 Aβ 和 tau 在胰腺中的积累以及大脑中胰岛淀粉样多肽的积累。而且，我们进行了邻位连接分析以确定 tau 和/或 Aβ 是否与这些受试者的胰腺或大脑中的胰淀素相互作用。结果 在患有 AD 的受试者以及神经病理学检查正常但有 T2DM 病史的受试者和一小群没有 T2DM 的对照受试者中检测到细胞质 tau 和 Aβ 蛋白沉积物。此外，我们在这些受试者的大脑中发现了胰淀素沉积物，提供了组织学证据表明胰淀素可以与胰腺和海马中的 Aβ 和 tau 相互作用。解读 胰腺 β 细胞中存在 tau 和 Aβ 内含物，以及大脑中存在胰淀素沉积，提供了新的证据表明 T2DM 和 AD 的潜在发病机制存在潜在重叠。ANN NEUROL 2019;86:539-551。