title: Upregulated Expression of Heparanase and Heparanase 2 in the Brains of Alzheimer's Disease.
abstract: Heparan sulfate proteoglycans (HSPGs) promote amyloid-β peptide and tau fibrillization in Alzheimer's disease (AD) and provide resistance against proteolytic breakdown. Heparanase (HPSE) is the only enzyme that cleaves heparan sulfate (HS). Heparanase 2 (HPSE2) lacks HS-degrading activity, although it is able to interact with HS with high affinity.
  
  
  
  To analyze HPSE and HPSE2 expressions at different stages of AD.
  
  
  
  RT-PCR was used to analyze transcription levels of both heparanases at different stages of AD, and immunohistochemistry was performed to localize each one in different parts of the brain.
  
  
  
  Both proteins appeared overexpressed at different stages of AD. Immunohistochemistry indicated that the presence of the heparanases was related to AD pathology, with intracellular deposits found in degenerated neurons. At the extracellular level, HPSE was observed only in neuritic plaques with a fragmented core, while HPSE2 appeared in those with compact cores as well.
  
  
  
  Given the involvement of HSPGs in AD pathology, there would seem to be a relationship between the regulation of heparanase expression, the features of the disease, and a possible therapeutic alternative.
authors.affiliation: Department of Functional Biology, University of Oviedo, Spain.|Instituto Universitario Fernández-Vega, Oviedo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: García
authors.affiliation: Department of Functional Biology, University of Oviedo, Spain.|Instituto Universitario Fernández-Vega, Oviedo, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Martín
authors.affiliation: Instituto Universitario Fernández-Vega, Oviedo, Spain.|Department of Morphology and Cell Biology, University of Oviedo, Oviedo, Spain.
authors.forename: Olivia
authors.initials: O
authors.lastname: García-Suárez
authors.affiliation: Department of Functional Biology, University of Oviedo, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Muñiz-Alonso
authors.affiliation: Department of Functional Biology, University of Oviedo, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Ordiales
authors.affiliation: Department of Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Fernández-Menéndez
authors.affiliation: Department of Pathology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Santos-Juanes
authors.affiliation: Department of Pathology, Hospital Universitario de Araba-Txagorritxu, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Lorente-Gea
authors.affiliation: Department of Biotechnology, Neiker-Tecnalia Arkaute, Vitoria-Gasteiz, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Castañón
authors.affiliation: Biobanco Vasco para la Investigación (O+eHun), Brain Bank, Hospital Universitario Araba, Spain.
authors.forename: Ikerne
authors.initials: I
authors.lastname: Vicente-Etxenausia
authors.affiliation: Department of Neurosurgery, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Kelvin Manuel
authors.initials: KM
authors.lastname: Piña Batista
authors.affiliation: Department of Pathology, Hospital Universitario Donostia, Gipuzkoa, Spain.
authors.forename: Irune
authors.initials: I
authors.lastname: Ruiz-Díaz
authors.affiliation: Department of Pathology, Hospital Universitario Donostia, Gipuzkoa, Spain.|Biobanco Vasco para la Investigación (O+eHun), Brain Bank Hospital Universitario Donostia, Spain.
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Caballero-Martínez
authors.affiliation: Instituto Universitario Fernández-Vega, Oviedo, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Merayo-Lloves
authors.affiliation: Department of Pathology, Hospital Universitario de Araba-Txagorritxu, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Guerra-Merino
authors.affiliation: Department of Functional Biology, University of Oviedo, Spain.|Instituto Universitario Fernández-Vega, Oviedo, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Quirós
authors.affiliation: Instituto Universitario Fernández-Vega, Oviedo, Spain.|Department of Pathology, Hospital Universitario Central de Asturias, Oviedo, Spain.|Department of Pathology, Hospital Universitario de Araba-Txagorritxu, Spain.|Biobanco Vasco para la Investigación (O+eHun), Brain Bank, Hospital Universitario Araba, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Fernández-Vega
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D001921:Brain / Q000201:enzymology*; D005260:Female; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D012333:RNA, Messenger; D000099175:Heparanase
keywords: Alzheimer’s disease; amyloid; amyloid-β; glycosaminoglycan; heparan sulfate; heparanase