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.
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.
| Original language | English |
|---|---|
| Article number | 79 |
| Pages (from-to) | 1-13 |
| Number of pages | 13 |
| Journal | Acta neuropathologica communications |
| Volume | 2 |
| DOIs | |
| Publication status | Published - 16 Jul 2014 |
