Tenascin-C Is Associated with Cored Amyloid-&bgr; Plaques in Alzheimer Disease and Pathology Burdened Cognitively Normal Elderly

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-&bgr; (A&bgr;) plaques and vascular A&bgr; 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 A&bgr; 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 A&bgr; 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 A&bgr; 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 A&bgr; 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 A&bgr; plaque pathogenesis and its potential as a biomarker and therapy target.

[1]  H. Paudel,et al.  14-3-3 binds to and mediates phosphorylation of microtubule-associated tau protein by Ser9-phosphorylated glycogen synthase kinase 3beta in the brain. , 2004, The Journal of biological chemistry.

[2]  D. Bennett,et al.  Entorhinal cortex beta-amyloid load in individuals with mild cognitive impairment. , 1999, Experimental neurology.

[3]  B. Penke,et al.  Tenascin-C deficiency ameliorates Alzheimer's disease-related pathology in mice , 2013, Neurobiology of Aging.

[4]  Giovanni B. Frisoni,et al.  Consensus report of the working group on: 'Molecular and biochemical markers of Alzheimer's disease' , 1998 .

[5]  S. Paul,et al.  Overexpression of the neuritotrophic cytokine S100beta precedes the appearance of neuritic beta-amyloid plaques in APPV717F mice. , 2000, Journal of neurochemistry.

[6]  John Seibyl,et al.  Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study , 2015, Alzheimer's & Dementia.

[7]  Y. Olsson,et al.  Amyloid angiopathy of the human brain: immunohistochemical studies using markers for components of extracellular matrix, smooth muscle actin and endothelial cells , 1998, Acta Neuropathologica.

[8]  C. Filley.  Diagnosis of Alzheimer's disease. , 1988, Colorado medicine.

[9]  P. Fraser,et al.  Review: modulating factors in amyloid-beta fibril formation. , 2000, Journal of structural biology.

[10]  J. Silver,et al.  Chondroitin Sulfate Proteoglycans Are Associated with the Lesions of Alzheimer's Disease , 1993, Experimental Neurology.

[11]  G. V. Van Hoesen,et al.  The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. , 1991, Cerebral cortex.

[12]  P. Taylor,et al.  Raised circulating tenascin-C in rheumatoid arthritis , 2012, Arthritis Research & Therapy.

[13]  A. Faissner,et al.  Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage , 2014, Front. Cell. Neurosci..

[14]  M. Chiquet,et al.  Transcriptional regulation of tenascin genes , 2015, Cell adhesion & migration.

[15]  I. Nikonenko,et al.  Glia and the Synapse: Plasticity and Disease , 2014, Neural Plasticity.

[16]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[17]  R. Coleman,et al.  Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study , 2012, The Lancet Neurology.

[18]  R. Chiquet‐Ehrismann,et al.  Tenascins and their implications in diseases and tissue mechanics , 2009, Scandinavian journal of medicine & science in sports.

[19]  R. Mrak,et al.  Interleukin‐1 Expression in Different Plaque Types in Alzheimer's Disease: Significance in Plaque Evalution , 1995, Journal of neuropathology and experimental neurology.

[20]  S. Zucker,et al.  Localization of Tissue Inhibitor of Matrix Metalloproteinases in Alzheimer's Disease and Normal Brain , 1995, Journal of neuropathology and experimental neurology.

[21]  G. Vollmer,et al.  Tenascin‐C in serum: A questionable tumor marker , 1995, International journal of cancer.

[22]  S. DeKosky,et al.  Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease. , 2007, Archives of neurology.

[23]  Charles D. Smith,et al.  Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease , 2009, Neurobiology of Aging.

[24]  L. V. Van Eldik,et al.  S100 beta expression in Alzheimer's disease: relation to neuropathology in brain regions. , 1994, Biochimica et biophysica acta.

[25]  P. Fraser,et al.  Review: Modulating Factors in Amyloid-β Fibril Formation , 2000 .

[26]  L. Beckett,et al.  Entorhinal Cortex β-Amyloid Load in Individuals with Mild Cognitive Impairment , 1999, Experimental Neurology.

[27]  M. Wolfe,et al.  A Portrait of Alzheimer Secretases--New Features and Familiar Faces , 2001, Science.

[28]  R. Veerhuis,et al.  Neuroinflammation in Plaque and Vascular β-Amyloid Disorders: Clinical and Therapeutic Implications , 2008, Neurodegenerative Diseases.

[29]  W. Halfter,et al.  Induction of tenascin in healing wounds , 1988, The Journal of cell biology.

[30]  Walter J Koroshetz,et al.  Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. , 2012, Archives of neurology.

[31]  George Perry,et al.  Senile plaque composition and posttranslational modification of amyloid-β peptide and associated proteins , 2002, Peptides.

[32]  R. Veerhuis,et al.  Goodpasture Antigen-binding Protein/Ceramide Transporter Binds to Human Serum Amyloid P-Component and Is Present in Brain Amyloid Plaques* , 2012, The Journal of Biological Chemistry.

[33]  D. Bouvier,et al.  Astrocyte-Secreted Matricellular Proteins in CNS Remodelling during Development and Disease , 2014, Journal of Neural Transplantation and Plasticity.

[34]  C. Masters,et al.  Amyloid plaque core protein in Alzheimer disease and Down syndrome. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[35]  W. Halfter,et al.  Agrin Binds to β-Amyloid (Aβ), Accelerates Aβ Fibril Formation, and Is Localized to Aβ Deposits in Alzheimer's Disease Brain , 2000, Molecular and Cellular Neuroscience.

[36]  M. Brown-Luedi,et al.  Tenascin-C signaling through induction of 14-3-3 tau , 2003, The Journal of cell biology.

[37]  J. Schneider,et al.  National Institute on Aging–Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease , 2012, Alzheimer's & Dementia.

[38]  R. Mrak,et al.  Neuritic plaque evolution in Alzheimer’s disease is accompanied by transition of activated microglia from primed to enlarged to phagocytic forms , 1997, Acta Neuropathologica.

[39]  P. Wesseling,et al.  Collagen XVIII: a Novel Heparan Sulfate Proteoglycan Associated with Vascular Amyloid Depositions and Senile Plaques in Alzheimer's Disease Brains , 2002, Brain pathology.

[40]  Paul Maruff,et al.  Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. , 2007, Brain : a journal of neurology.

[41]  J. Lowe,et al.  Neurofibrillary tangles of Alzheimer's disease brains contain 14-3-3 proteins , 1996, Neuroscience Letters.

[42]  T. Wyss-Coray,et al.  Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. , 2012, Cold Spring Harbor perspectives in medicine.

[43]  H. Paudel,et al.  14-3-3ζ Is an Effector of Tau Protein Phosphorylation* , 2000, The Journal of Biological Chemistry.

[44]  H. Paudel,et al.  14-3-3 Binds to and Mediates Phosphorylation of Microtubule-associated Tau Protein by Ser9-phosphorylated Glycogen Synthase Kinase 3β in the Brain* , 2004, Journal of Biological Chemistry.

[45]  I. Kanazawa,et al.  CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC‐P/collagen type XXV , 2002, The EMBO journal.

[46]  C. Plata-salamán,et al.  Inflammation and Alzheimer’s disease , 2000, Neurobiology of Aging.

[47]  D. Nochlin,et al.  Identification in immunolocalization of a new class of proteoglycan (keratan sulfate) to the neuritic plaques of Alzheimer's disease. , 1996, Experimental neurology.

[48]  A. Bhattacharyya,et al.  Tenascin in normal, reactive, hyperplastic, and neoplastic tissues: biologic and pathologic implications. , 1991, Human pathology.

[49]  V. Libri,et al.  PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. , 2007, Brain : a journal of neurology.

[50]  D. Steindler,et al.  Enhanced expression of the developmentally regulated extracellular matrix molecule tenascin following adult brain injury. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[51]  D. Nochlin,et al.  Identification and Immunolocalization of a New Class of Proteoglycan (Keratan Sulfate) to the Neuritic Plaques of Alzheimer's Disease , 1996, Experimental Neurology.

[52]  D. Miller,et al.  Tenascin expression in astrocytomas correlates with angiogenesis. , 1995, Cancer research.

[53]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[54]  Paul Maruff,et al.  β-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease , 2007 .

[55]  J. Krebs,et al.  Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[56]  W. Griffin,et al.  Overexpression of the Neuritotrophic Cytokine S100β Precedes the Appearance of Neuritic β‐Amyloid Plaques in APPV717F Mice , 2000 .

[57]  Shigeki,et al.  Tenascin: cDNA cloning and induction by TGF‐beta. , 1988, The EMBO journal.

[58]  Ranjan Duara,et al.  Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density. , 2015, JAMA neurology.

[59]  George M. Smith,et al.  Macrophage/Microglia Regulation of Astrocytic Tenascin: Synergistic Action of Transforming Growth Factor-β and Basic Fibroblast Growth Factor , 1997, The Journal of Neuroscience.

[60]  H. Kresse,et al.  Peripheral distribution of dermatan sulfate proteoglycans (decorin) in amyloid-containing plaques and their presence in neurofibrillary tangles of Alzheimer's disease. , 1992, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[61]  S. Weis,et al.  Expression of tenascin‐C in various human brain tumors and its relevance for survival in patients with astrocytoma , 2003, Cancer.

[62]  Keith A. Johnson,et al.  Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. , 2007, Archives of neurology.

[63]  N. Bruno,et al.  Deficiency of tenascin C attenuates allergen‐induced bronchial asthma in the mouse , 2006, European journal of immunology.

[64]  H. Paudel,et al.  14-3-3 Connects Glycogen Synthase Kinase-3β to Tau within a Brain Microtubule-associated Tau Phosphorylation Complex* , 2003, The Journal of Biological Chemistry.

[65]  D. A. Bennett,et al.  Natural history of mild cognitive impairment in older persons , 2002, Neurology.

[66]  P. Eikelenboom,et al.  The neuroinflammatory response in plaques and amyloid angiopathy in Alzheimer's disease: therapeutic implications , 2005 .

[67]  S. DeKosky,et al.  X-34 labeling of abnormal protein aggregates during the progression of Alzheimer's disease. , 2006, Methods in enzymology.

[68]  I. Knuesel,et al.  Co-localization of Reelin and proteolytic AbetaPP fragments in hippocampal plaques in aged wild-type mice. , 2010, Journal of Alzheimer's disease : JAD.

[69]  R. Mrak,et al.  Correlation of Astrocytic S100β Expression with Dystrophic Neurites in Amyloid Plaques of Alzheimer's Disease , 1996, Journal of neuropathology and experimental neurology.

[70]  W. Halfter,et al.  Agrin binds to beta-amyloid (Abeta), accelerates abeta fibril formation, and is localized to Abeta deposits in Alzheimer's disease brain. , 2000, Molecular and cellular neurosciences.

[71]  D. Nochlin,et al.  The presence of heparan sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer's disease. , 1988, The American journal of pathology.

[72]  K. Grzeschik,et al.  The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor , 1987, Nature.

[73]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[74]  R. Tucker,et al.  Tenascins and the importance of adhesion modulation. , 2011, Cold Spring Harbor perspectives in biology.

[75]  S. DeKosky,et al.  Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease , 2008, Brain : a journal of neurology.

[76]  L. Zardi,et al.  Comparative analysis of the expression of the extracellular matrix protein tenascin in normal human fetal, adult and tumor tissues , 1991, International journal of cancer.

[77]  W. Klunk,et al.  Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B , 2004, Annals of neurology.

[78]  S. M. Sumi,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1991, Neurology.

[79]  B. Maras,et al.  14‐3‐3ε marks the amyloid‐stimulated microglia long‐term activation , 2012, Proteomics.

[80]  M. Kashiwagi,et al.  Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease , 2009, Nature Medicine.