The Beta Amyloid Core Hexapeptide Protects against Full-Length Beta Amyloid-Induced Alteration of Dendritic Spine Morphology and Density.

Abstract

Pathological levels of beta amyloid (Aβ) lead to disruption and elimination of synapses in brain as the result of direct neurotoxicity as well as neuroinflammation. The synaptic impact of beta amyloid includes altered morphology and reduced number of dendritic spines at excitatory synapses, evident in the brains of individuals with Alzheimer's disease. Here, we assessed the ability of an identified neuroprotective peptide, YEVHHQ, derived from the N-terminal domain of Aβ, known as the AβCore, to protect against Aβ-induced alterations in dendritic spines. Our approach involved both 2D and 3D imaging of spine morphology in hippocampal neuron cultures from mice of either sex, with the 3D imaging focusing on the postsynaptic density (PSD), as its morphology is tightly correlated with synaptic strength, and presynaptic terminal morphology and density to assess the impact on both sides of the synapse. We present evidence for uniform prevention by the AβCore of Aβ-induced reductions in spine cross-sectional size and density as well as PSD surface area and volume. In addition, the AβCore alone increased the presynaptic terminal volume in parallel to the reversal of Aβ-induced changes in spine and PSD size. Together, these results provide support for reversal of structural changes underlying the functional reversal by the AβCore of Aβ-induced impairment of synaptic dynamics.