Biochemical analyses of tau and other neuronal markers in the submandibular gland and frontal cortex across stages of Alzheimer disease

• Published in: Neuroscience letters 2023-07, Vol.810, p.137330, Article 137330
• Main Authors: Hamsafar, Yamah, Chen, Qian, Borowsky, Alexander D., Beach, Thomas G., Serrano, Geidy E., Sue, Lucia I., Adler, Charles H., Walker, Douglas G., Dugger, Brittany N.
• Format: Article
• Language: English
• Subjects: 4a exon; Alzheimer Disease - metabolism; Big tau; Frontal Lobe - metabolism; Humans; Microtubule-associated protein 2; Neurofibrillary Tangles - metabolism; Neurofilament heavy chain; Neurons - metabolism; Phosphorylated tau (p-tau); Phosphorylation; Submandibular gland; Submandibular Gland - metabolism; Submandibular Gland - pathology; Tau; tau Proteins - metabolism; Tyrosine hydroxylase
• ISSN: 0304-3940; 1872-7972; 1872-7972
• DOI: 10.1016/j.neulet.2023.137330

•Select tau species and other neuronal proteins are detected in the submandibular gland of human cases.•The evaluated neuronal proteins experience differential protein levels based on anatomic region (submandibular gland or frontal cortex) and clinicopathological stage of AD.•Tissues innervated by the peripheral nervous system may experience unique selective vulnerabilities in AD. 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.