title: Tenascin-C Is Associated with Cored Amyloid-β Plaques in Alzheimer Disease and Pathology Burdened Cognitively Normal Elderly.
abstract: Tenascin-C (TN-C) is an extracellular matrix glycoprotein linked to inflammatory processes in pathological conditions including Alzheimer disease (AD). We examined the distribution of TN-C immunoreactivity (ir) in relation to amyloid-β (Aβ) plaques and vascular Aβ deposits in autopsy brain tissues from 14 patients with clinical and neuropathological AD and 10 aged-matched controls with no cognitive impairment; 5 of the controls had Aβ plaques and 5 did not. TN-C ir was abundant in cortical white matter and subpial cerebral gray matter in all cases, whereas TN-C ir was weak in blood vessels. In all cases with Aβ plaques but not in plaque-free controls, TN-C ir was detected as large (>100 µm in diameter) diffuse extracellular deposits in cortical grey matter. TN-C plaques completely overlapped and surrounded cored Aβ plaques labeled with X-34, a fluorescent derivative of Congo red, and they were associated with reactive astrocytes astrocytes, microglia and phosphorylated tau-containing dystrophic neurites. Diffuse Aβ plaques lacking amyloid cores, reactive glia or dystrophic neurites showed no TN-C ir. In cases with cerebral amyloid angiopathy, TN-C ir in vessel walls did not spread into the surrounding neuropil. These results suggest a role for TN-C in Aβ plaque pathogenesis and its potential as a biomarker and therapy target.
authors.affiliation: From the Departments of Neurology (ZM, EEA, WEK, MDI)Department of Neurobiology (WH)Department of Psychiatry (WEK, MDI)Department of Radiology, University of Pittsburgh (CAM)Department of Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System (ZM, EEA, MDI)Department of Neurobiology, Barrow Neurological Institute, Pittsburgh, PA, USA (EJM).
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Mi
authors.affiliation: From the Departments of Neurology (ZM, EEA, WEK, MDI)Department of Neurobiology (WH)Department of Psychiatry (WEK, MDI)Department of Radiology, University of Pittsburgh (CAM)Department of Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System (ZM, EEA, MDI)Department of Neurobiology, Barrow Neurological Institute, Pittsburgh, PA, USA (EJM).
authors.forename: Willi
authors.initials: W
authors.lastname: Halfter
authors.affiliation: From the Departments of Neurology (ZM, EEA, WEK, MDI)Department of Neurobiology (WH)Department of Psychiatry (WEK, MDI)Department of Radiology, University of Pittsburgh (CAM)Department of Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System (ZM, EEA, MDI)Department of Neurobiology, Barrow Neurological Institute, Pittsburgh, PA, USA (EJM).
authors.forename: Eric E
authors.initials: EE
authors.lastname: Abrahamson
authors.affiliation: From the Departments of Neurology (ZM, EEA, WEK, MDI)Department of Neurobiology (WH)Department of Psychiatry (WEK, MDI)Department of Radiology, University of Pittsburgh (CAM)Department of Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System (ZM, EEA, MDI)Department of Neurobiology, Barrow Neurological Institute, Pittsburgh, PA, USA (EJM).
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: From the Departments of Neurology (ZM, EEA, WEK, MDI)Department of Neurobiology (WH)Department of Psychiatry (WEK, MDI)Department of Radiology, University of Pittsburgh (CAM)Department of Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System (ZM, EEA, MDI)Department of Neurobiology, Barrow Neurological Institute, Pittsburgh, PA, USA (EJM).
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.affiliation: From the Departments of Neurology (ZM, EEA, WEK, MDI)Department of Neurobiology (WH)Department of Psychiatry (WEK, MDI)Department of Radiology, University of Pittsburgh (CAM)Department of Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System (ZM, EEA, MDI)Department of Neurobiology, Barrow Neurological Institute, Pittsburgh, PA, USA (EJM).
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.affiliation: From the Departments of Neurology (ZM, EEA, WEK, MDI)Department of Neurobiology (WH)Department of Psychiatry (WEK, MDI)Department of Radiology, University of Pittsburgh (CAM)Department of Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System (ZM, EEA, MDI)Department of Neurobiology, Barrow Neurological Institute, Pittsburgh, PA, USA (EJM) ikonomovicmd@upmc.edu.
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D003071:Cognition / Q000502:physiology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D058225:Plaque, Amyloid / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D019063:Tenascin / Q000032:analysis*
chemical_list: D016229:Amyloid beta-Peptides; D019063:Tenascin
keywords: Alzheimer disease; Astrocytes; Extracellular matrix; Inflammation; Microglia; Tau; Tenascin; β-amyloid