Synaptic loss in a mouse model for Alzheimer’s disease
Nature Neuroscience
December 13, 2010
An early pathological process that leads to synaptic loss and decline of cognitive ability in a mouse model of Alzheimer's disease is unraveled in a paper online this week in Nature Neuroscience. This early pathology could be inhibited by a small molecule drug.
Francesco Cecconi and colleagues studied mice that carry a mutated gene known to cause a hereditary form of Alzheimer's disease in people. At the age of three months, these mice lose the ability to remember a threatening environment. The group found that at the same age, the enzyme caspase-3 was activated in the mice's hippocampus ― a brain structure crucial to memory. Caspase-3 is a trigger of nerve cell death, however in this case no hippocampal neurons died. Instead, caspase-3 activity, via activation of a second enzyme, caused the removal of crucial receptor molecules from hippocampal synapses, thereby impairing synapse function. They show that inhibitor of caspase-3 prevented receptor loss from the synapses, and conserved the mice's ability to remember a cage where they had received painful electric shocks.
It remains to be tested, however, whether a caspase-3-dependent mechanism is also responsible for memory decline in early stage Alzheimer's patients, and whether inhibitors of caspase-3 might slow progress of the disease in people.
doi: 10.1038/nn.2709
Research highlights
-
Jul 1
Criminology: Predicting police enforcement bias in major US citiesNature Human Behaviour
-
Jul 1
Evolution: Pandas gave bamboo the thumbs up at least six million years agoScientific Reports
-
Jul 1
Space health: The path of most resistance could help limit bone loss during spaceflightScientific Reports
-
Jun 30
Genomics: Gray wolf genome hints at dual ancestry of dogsNature
-
Jun 30
Evolution: Hawks learn on the fly to swoop up before perchingNature
-
Jun 30
Microbiology: Transmission of gastrointestinal viruses in salivaNature