Carrying a particular version of the gene for apolipoprotein E (APOE) is the major known genetic risk factor for the sporadic, late-onset form of Alzheimer's disease, but exactly how that variant confers increased risk has been controversial among researchers. Now an animal study led by Massachusetts General Hospital (MGH) investigators shows that even low levels of the Alzheimer's-associated APOE4 protein can increase the number and density of amyloid beta (A-beta) brain plaques, characteristic neuronal damage, and the amount of toxic soluble A-beta within the brain in mouse models of the disease. Introducing APOE2, a rare variant that has been associated with protection from developing Alzheimer's disease, into the brains of animals with established plaques actually reduced A-beta deposition, retention and neurotoxicity, suggesting the potential for gene-therapy-based treatment.
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