BIN1 Genetic Risk Factor for Alzheimer is Sufficient to Induce Early Structural Tract Alterations in Entorhinal-Hippocampal Area and Memory-Related Hippocampal Multi-Scale Impairments

A systems biology-based identification and in vivo functional screening of Alzheimer’s disease risk genes reveals modulators of memory function

“…Additionally, recent work has shown that neuron-specific conditional knockout of BIN1 results in reduced synapse density, decreased presynaptic vesicle release, and learning and memory deficits in mice 67 . Interestingly, we found that neuronalspecific knockdown of the C. elegans ortholog amph-1 (BIN1) resulted in a decreased ability to "forget" an associated memory, in line with its role in RAC1-mediated synaptic remodeling 80 , an important component in the process of active forgetting 77,78 . These results suggest complex roles for neuronal BIN1 function that may have isoform-dependent phenotypes upon perturbation.…”

“…Interestingly, we found that neuronal-specific knockdown of the C . elegans ortholog amph-1 ( BIN1 ) resulted in a decreased ability to “forget” an associated memory, in line with its role in RAC1-mediated synaptic remodeling 80 , an important component in the process of active forgetting 77,78 . These results suggest complex roles for neuronal BIN1 function that may have isoform-dependent phenotypes upon perturbation.…”

“…These results indicate that neuronal loss of expression of these genes impacts processes of active forgetting that are mediated through RAC1/CDC42 77,78 . Indeed, NGEF encodes a neuronal guanine nucleotide exchange factor (GEF) that regulates the activity of GTPases such as RAC1, RHOA, and CDC42 79 , and recent work has implicated BIN1 in RAC1-mediated synaptic remodeling 80 .…”