Upregulated Expression of Heparanase and Heparanase 2 in the Brains of Alzheimer's Disease

作者：Garcia Beatriz; Martin Carla; Garcia Suarez Olivia; Muniz Alonso Barbara; Ordiales Helena; Fernandez Menendez Santiago; Santos Juanes Jorge; Lorente Gea Laura; Castanon Sonia; Vicente Etxenausia Ikerne; Pina Batista Kelvin Manuel; Ruiz Diaz Irune; Cristina Caballero Martinez Maria; Merayo Lloves Jesus; Guerra Merino Isabel; Quiros Luis M; Fernandez Vega Ivan^*

来源：Journal of Alzheimer's Disease, 2017, 58(1): 185-192.

DOI：10.3233/JAD-161298

• Alzheimer's disease
• amyloid
• amyloid-beta
• glycosaminoglycan
• heparan sulfate
• heparanase

Background: Heparan sulfate proteoglycans (HSPGs) promote amyloid-beta 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.
Objective: To analyze HPSE and HPSE2 expressions at different stages of AD.
Methods: 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.
Results: 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.
Conclusion: 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.

• 出版日期2017