Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, 4400 V Street, Sacramento, CA 95817, USA.
Banner Sun Health Research Institute, 10515 W Santa Fe Dr., Sun City, AZ 95351, USA.
Neurosci Lett. 2023 Jul 27;810:137330. doi: 10.1016/j.neulet.2023.137330. Epub 2023 Jun 16.
Hyperphosphorylation of the microtubule-associated protein tau is hypothesized to lead to the development of neurofibrillary tangles in select brain regions during normal aging and in Alzheimer disease (AD). The distribution of neurofibrillary tangles is staged by its involvement starting in the transentorhinal regions of the brain and in final stages progress to neocortices. However, it has also been determined neurofibrillary tangles can extend into the spinal cord and select tau species are found in peripheral tissues and this may be depended on AD disease stage. To further understand the relationships of peripheral tissues to AD, we utilized biochemical methods to evaluate protein levels of total tau and phosphorylated tau (p-tau) as well as other neuronal proteins (i.e., tyrosine hydroxylase (TH), neurofilament heavy chain (NF-H), and microtubule-associated protein 2 (MAP2)) in the submandibular gland and frontal cortex of human cases across different clinicopathological stages of AD (n = 3 criteria not met or low, n = 6 intermediate, and n = 9 high likelihood that dementia is due to AD based on National Institute on Aging-Reagan criteria). We report differential protein levels based on the stage of AD, anatomic specific tau species, as well as differences in TH and NF-H. In addition, exploratory findings were made of the high molecular weight tau species big tau that is unique to peripheral tissues. Although sample sizes were small, these findings are, to our knowledge, the first comparison of these specific protein changes in these tissues.
在正常衰老和阿尔茨海默病（AD）中，微管相关蛋白 tau 的过度磷酸化被认为会导致特定脑区神经原纤维缠结的发展。神经原纤维缠结的分布通过其在脑的transentorhinal 区的参与进行分期，并且在最后阶段进展到新皮质。然而，也已经确定神经原纤维缠结可以延伸到脊髓，并且在周围组织中发现了选择的 tau 物种，这可能取决于 AD 疾病阶段。为了进一步了解周围组织与 AD 的关系，我们利用生化方法评估了总 tau 和磷酸化 tau（p-tau）以及其他神经元蛋白（即酪氨酸羟化酶（TH）、神经丝重链（NF-H）和微管相关蛋白 2（MAP2））在人类下颌下腺和前额皮质中的蛋白水平在 AD 的不同临床病理阶段（n = 3 不符合标准或低标准，n = 6 中度，n = 9 高可能性痴呆是由于基于国家老龄化研究所-里根标准的 AD）。我们根据 AD 的阶段、解剖学特异性 tau 物种以及 TH 和 NF-H 的差异报告了差异蛋白水平。此外，还对周围组织特有的高分子量 tau 物种 big tau 进行了探索性发现。尽管样本量较小，但这些发现是我们所知的这些组织中这些特定蛋白质变化的首次比较。
