title: The Presence of Select Tau Species in Human Peripheral Tissues and Their Relation to Alzheimer's Disease.
abstract: Tau becomes excessively phosphorylated in Alzheimer's disease (AD) and is widely studied within the brain. Further examination of the extent and types of tau present in peripheral tissues and their relation to AD is warranted given recent publications on pathologic spreading. Cases were selected based on the presence of pathological tau spinal cord deposits (n = 18). Tissue samples from sigmoid colon, scalp, abdominal skin, liver, and submandibular gland were analyzed by western blot and enzyme-linked immunosorbent assays (ELISAs) for certain tau species; frontal cortex gray matter was used for comparison. ELISAs revealed brain to have the highest total tau levels, followed by submandibular gland, sigmoid colon, liver, scalp, and abdominal skin. Western blots with antibodies recognizing tau phosphorylated at threonine 231(pT231), serine 396 and 404 (PHF-1), and an unmodified total human tau between residues 159 and 163 (HT7) revealed multiple banding patterns, some of which predominated in peripheral tissues. As submandibular gland had the highest levels of peripheral tau, a second set of submandibular gland samples were analyzed (n = 36; 19 AD, 17 non-demented controls). ELISAs revealed significantly lower levels of pS396 (p = 0.009) and pT231 (p = 0.005) in AD cases but not total tau (p = 0.18). Furthermore, pT231 levels in submandibular gland inversely correlated with Braak neurofibrillary tangle stage (p = 0.04), after adjusting for age at death, gender, and postmortem interval. These results provide evidence that certain tau species are present in peripheral tissues. Of potential importance, submandibular gland pT231 is progressively less abundant with increasing Braak neurofibrillary tangle stage.
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Dugger
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Charisse M
authors.initials: CM
authors.lastname: Whiteside
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Chera L
authors.initials: CL
authors.lastname: Maarouf
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Walker
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Lucia I
authors.initials: LI
authors.lastname: Sue
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Angelica
authors.initials: A
authors.lastname: Garcia
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Travis
authors.initials: T
authors.lastname: Dunckley
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Bessie
authors.initials: B
authors.lastname: Meechoovet
authors.affiliation: Banner Alzheimer's Institute, Phoenix, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.|Arizona Alzheimer's Consortium.
authors.forename: Alex E
authors.initials: AE
authors.lastname: Roher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D003106:Colon / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D066128:Gray Matter / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012720:Severity of Illness Index; D012727:Sex Characteristics; D012867:Skin / Q000378:metabolism*; D013363:Submandibular Gland / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: Braak NFT stage; PHF-1; T231; colon, HT7; liver; propagation; skin; spread; submandibular gland