Neurology Department, Clínica Universidad de Navarra, Pamplona, Spain.
Regenerative Therapy Laboratory, Neurosciences Division, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
Ann Neurol. 2019 Oct;86(4):539-551. doi: 10.1002/ana.25570. Epub 2019 Aug 19.
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.
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.
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.
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.
阿尔茨海默病（AD）是痴呆症的主要病因，尽管其病因仍不清楚，但 2 型糖尿病（T2DM）和其他胰岛素抵抗的前驱糖尿病状态似乎可能导致散发性 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，以及作为 T2DM 患者胰腺中沉积的淀粉样蛋白的胰岛淀粉样多肽（amylin）是否可能在 AD 患者的大脑中蓄积。
我们研究了 48 名无神经病理学改变的个体和 87 名被诊断为 AD 的个体的胰腺和脑组织。我们检查了胰腺中 Aβ和 tau 的积累以及大脑中 amylin 的积累。此外，我们进行了邻近连接测定，以确定 tau 和/或 Aβ是否在这些受试者的胰腺或大脑中与 amylin 相互作用。
AD 患者的胰腺β细胞以及具有正常神经病理学检查但有 T2DM 病史的个体和一小部分无 T2DM 的对照个体中均检测到细胞质 tau 和 Aβ蛋白沉积。此外，我们在这些受试者的大脑中发现了 amylin 沉积，提供了组织学证据表明 amylin 可以在胰腺和海马体中与 Aβ和 tau 相互作用。
在胰腺β细胞中存在 tau 和 Aβ包涵体，以及在大脑中存在 amylin 沉积，为 T2DM 和 AD 发病机制潜在重叠的机制提供了新的证据。ANN NEUROL 2019;86:539-551。
