Neurology Central

Novel gene therapy approach to Alzheimer’s

A new study has shown evidence of significant repair of synapse damage in mouse models of Alzheimer’s disease. The study, which focused on the delivery of APPsα to the brain, highlights potential new approaches to the development of novel gene therapies for Alzheimer’s. Results were published in Acta Neuropathologica recently.

The research team concentrated on APP and its cleavage product APPsα, which has been highlighted as a potential protective agent against the neurotoxicity of beta amyloid peptides. “Research over the last few years indicates that a misregulation of the secretase cleavage in Alzheimer’s results in inadequate production of protective APPsα,” explained Ulrike Müller (University of Heidelberg), lead author of the study.

Earlier studies by Müller’s team also indicated that APPsα may have an essential role in the nervous system, especially in the regulation of the formation and functioning of synaptic junctions and spatial memory. Utilizing viral gene shuttles, APPsα was delivered into the brains of APP/PS1∆E9 Alzheimer’s Disease mouse models.

Müller explained their findings: “After introducing the APPsα, we saw that the nerve cell damage could be repaired. The number of synaptic junctions increased, and spatial memory began to function again.” This was illustrated through improved synaptic plasticity and partially rescued spine density deficits as well as improvements in the responses to the Morris water maze.

In addition to this, a significant reduction of soluble Aβ species and plaque load was recorded, as well as an increase in the recruitment of branched microglia within the vicinity of plaques and upregulated IDE and TREM2 expression. All of which suggested an increased clearance of amyloid plaques.

The findings highlight the possible therapeutic efficacy of APPsα for the treatment of Alzheimer’s Disease and potential new avenues for gene therapy research.

Source: University of Heidelberg press release; Fol R et al. Viral gene transfer of APPsα rescues synaptic failure in an Alzheimer’s disease mouse model. Acta Neuropathologica, DOI: 10.1007/s00401-015-1498-9 (2015).