Synaptic β-amyloid precursor proteins increase with learning capacity in rats

Abstract

The precursor proteins of Alzheimer's disease β-amyloid peptide, the β-amyloid precursor protein isoforms, comprise a family of neuronal proteins with synaptic localization whose physiological roles in brain are poorly understood. One possible role for synaptic proteins is involvement in neuronal plasticity. After exposure to an enriched environment compared to impoverished conditions, rats exhibited superior cognitive capacity. Up to ∼four-fold increased overall levels of β-amyloid precursor proteins were found in cortical/subcortical tissue of the enriched animals displaying significantly more synapses immunoreactive for the different β-amyloid precursor protein isoforms ( β-amyloid precursor protein 695- and β-amyloid precursor protein 751/770) in hippocampus and adjacent occipital cortex. This correlation thus provides in vivo evidence for an association of β-amyloid precursor proteins with plastic changes induced by complex environment with consequences for cognitive functions and suggests that impaired β-amyloid precursor protein metabolism at synapses might contribute to brain dysfunction in Alzheimer's disease.