title: Altered distribution of the EphA4 kinase in hippocampal brain tissue of patients with Alzheimer's disease correlates with pathology.
abstract: Synaptic dysfunction occurs early in the progression of Alzheimer's disease (AD) and correlates with memory decline. There is emerging evidence that deregulation of Erythropoietin-producing hepatocellular (Eph) receptor tyrosine kinases (RTK) signaling contributes to the aberrant synaptic functions associated with neurodegeneration. The Eph receptor A4 is highly expressed in human adult hippocampal brain tissue and was previously linked to cognitive impairment in a transgenic mouse model for AD. Whether EphA4 levels are altered in AD brain remains elusive. Therefore we investigated the protein levels and localization of EphA4 in human hippocampus derived from AD (n = 29) as well as non-demented control cases (n = 19). The total EphA4 protein levels were not changed in AD patients compared to control cases. However, immunohistochemical localization of EphA4 revealed an altered distribution in AD compared to control hippocampus. EphA4 immunoreactivity was observed in plaque-like structures in AD cases. Double-labelling with phosphorylated tau and amyloid beta indicates that EphA4 co-localizes with neuritic plaques in AD. This altered distribution pattern was observed at early stages (Braak stage II) and correlates with the hallmarks of AD pathology suggesting a reduced availability of EphA4 that is likely to contribute to synaptic dysfunction that occurs early in AD.
authors.forename: Andrea Fn
authors.initials: AF
authors.lastname: Rosenberger
authors.forename: Annemieke Jm
authors.initials: AJ
authors.lastname: Rozemuller
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Saskia M
authors.initials: SM
authors.lastname: van der Vies
authors.forename: Jeroen Jm
authors.initials: JJ
authors.lastname: Hoozemans
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000378:metabolism; D036122:Receptor, EphA4 / Q000032:analysis / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; D036122:Receptor, EphA4