P3‐181: The Interaction Between Tau and Protein Phosphatase 1 Is Affected by P301l Mutation

Abstract

Background: Many studies on Alzheimer's disease (AD) focus solely on how neuronal proteins change in the brain, so little is known about what is happening to these same proteins in peripheral tissues. For example, it is known that tau is present within the human submandibular gland and that levels of some tau variants are inversely relate to Braak neurofibrillary tangle (NFT) stage. However, it is unclear if other neuronal proteins may also be detected in the submandibular gland and whether their levels are also disrupted. Such insights may provide new knowledge of the mechanisms of selective vulnerability and aid in developing better model systems and treatments. Methods: Submandibular glands were collected from human autopsy cases of AD (N¼17) and nondemented individuals (ND, N¼16). Biochemical and immunohistochemical methods were performed with markers for neuronal proteins including neurofilament, tyrosine hydroxylase (TH), and choline acetyl transferase (ChAT), in addition to select tau antibodies. Human brain samples of AD and ND cases were utilized as controls. Results: Biochemically, neurofilament, TH, and ChAT although present within the submandibular gland, did not appear to be altered by AD status, Braak NFT stage, nor correlated to tau levels. With respect to immunohistochemistry, neurofilament and TH were mainly within stromal nerve fascicles, while ChAT was mainly located within connective tissues proximal to blood vessels and ducts. Although neither neurofilament, TH, or ChAT had complete colocalization, all three did have some colocalization with select tau antibodies. Conclusions: These preliminary results demonstrate that neurofilament, TH, and ChAT can be detected within submandibular glands, although their levels do not appear to be altered based on AD status. Their co-localization with tau provides additional evidence that tau within the periphery is neuronal in nature.