Abstract
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and the most common cause of elderly dementia. One of the main features of AD diseased brain are amyloid plaques, pathological depositions made of β-amyloid peptide, derived from β- amyloid precursor protein (APP). To assess how AD pathology affects synapses in the hippocampus, brain region to be one of the earliest with obvious pathological changes, we examined APPPS1 mice, transgeneticaly expressing human APP mutation (“Swedish mutation”) and human presenilin-1 mutation under the neuron-specific promoter, which develop AD symptoms early in life. We analyzed inhibitory and excitatory synapses using immunoflourescent staining and laser scanning confocal microscopy. In APPPS1 mice, inhibitory synaptic terminals labeled with vesicular inhibitory transmitter transporter (VGAT) were reduced in CA1 and CA3 regions of the hippocampus in APPPS1 mice compared to controls. This was true for both parvalbumin-positive and parvalbumin-negative terminals. On the other hand, excitatory synapses, coming from either hippocampal or entorhinal projections were similar between the genotypes. We conclude that first changes in the hippocampus caused by amyloid pathology affect inhibitory, but not excitatory synapses.