Today, no disease-modifying therapy for AD is available. The hypothesis that amyloid-β peptide plays an early causative role in disease progression is supported by pathology, human genetics and biomarker studies. Ongoing clinical trials with technologies aimed directly at reducing amyloid-β levels in the human brain have largely failed.
Recent advances in our understanding of AD have pointed to amyloid-β oligomers as a distinctly toxic species, differentiated from soluble, fibril or plaque forms. As symptomatic patients already have saturating levels of amyloid-β in their brain, methods targeting removal of this toxic species are proving inadequate. There is an urgent need to develop new approaches to AD and strategies distinct from amyloid-lowering.
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein
Metabotropic Glutamate Receptor 5 Couples Cellular Prion Protein to Intracellular Signalling in Alzheimer’s Disease
Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes