title: Alzheimer's disease and retinal neurodegeneration share a consistent stress response of the neurovascular unit.
abstract: BACKGROUND
  The pathogenesis of Alzheimer's disease (AD) is characterized by neuronal injury, activation of microglia and astrocytes, deposition of amyloid-β and secondary vessel degeneration. In the polycystic kidney disease (PKD) rat model, we observed neuronal injury, microglial activation and vasoregression. We speculated that this neuroretinal degeneration shares important pathogenetic steps with AD. Therefore, we determined the activation of astrocytes and the accumulation of amyloid-β in PKD retinae.
  
  
  METHODS
  Immunohistochemistry of PKD retinae for vimentin, carboxymethyllysin, beta-Amyloid 1-42, High-Mobility-Group- Protein B1 and amyloid protein precursor was performed.
  
  
  RESULTS
  Adjunct to astrocyte activation, accumulation of beta-Amyloid 1-42 and High-Mobility-Group-Protein B1 in astrocytes and around vessels of the superficial network was found in PKD retinae prior to the onset of vasoregression. Amyloid precursor protein was localized adjacent to the outer segment of photoreceptors in PKD and control rats. The parallel appearance of AD-related peptides indicates an alarmine based response to photoreceptor degeneration and secondary vasoregression.
  
  
  CONCLUSIONS
  The model has broad overlap with AD and may be suitable to study beneficial pharmacological concepts.
authors.affiliation: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. StephanieBusch@web.de
authors.forename: Stephanie
authors.initials: S
authors.lastname: Busch
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Feng
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009457:Neuroglia / Q000378:metabolism; D007690:Polycystic Kidney Diseases / Q000150:complications / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D012171:Retinal Vessels / Q000473:pathology / Q000503:physiopathology*; D013312:Stress, Physiological; D014746:Vimentin / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D014746:Vimentin