Authors: Alice Weatherston
New findings presented today at Neuroscience 2015 (17 – 21 October, Chicago, IL) have demonstrated that amyloid-beta Aβ may not be the only contributor to Alzheimer’s disease pathology. The study highlights the protein fragment, termed APP intracellular domain (AICD), as another potential cause of Alzheimer’s toxicity and damage, and indicates a new avenue for research into the disease.
The research team based at CNRS (Valbonne, France) focused their investigation on the relatively little known amyloid precursor protein (APP) fragment AICD, which is formed in the same enzymatic process as Aβ. Despite its clear presence relatively little is understood about its role within the hippocampus.
Following the use of a virus to increase production of AICD in vivo in adult CA1 pyramidal neurons, the team then utilized a range of electrophysiological and pharmacological approaches to assess signaling in pairs of neurons within the hippocampus.
Results indicated that neurons containing an increased level of AICD also possessed increased synaptic NMDA receptor currents and were unable to integrate incoming signals. Impaired long-term potentiation was also exhibited. The administration of pharmacological treatments however, resulted in the normalization of synapse receptors.
“Identification of additional culprits participating in Alzheimer’s disease-related neurotoxicity and memory loss could provide crucial new insights into disease mechanism and help design innovative therapies,” commented lead author Paula Pousinha of CNRS in Valbonne, France.
She continued: “Our results provide entirely novel evidence that increased in vivo production of AICD alone is enough to perturb synapse function in hippocampal neurons. These data suggest that, in addition to Aβ, AICD could also participate in the disruption of synaptic communication during the progression of Alzheimer’s disease.”
Source: Neuroscience 2015 press release. The full astract can be found here