WASHINGTON (Dispatches) -- Changing the biochemistry of parts of brain cells abolished the formation of amyloid beta plaques in a mouse model of Alzheimer’s disease, a study reports.
Alzheimer’s disease is characterized by brain cells plagued by extracellular plaques made of a protein called amyloid beta and intracellular tangles made of an abnormal form of a protein called tau. Although the causes of the disease are not well defined, scientists have long known that the most significant genetic risk factor for late-onset Alzheimer’s is apolipoprotein E4 (ApoE4), one of three variants of a protein involved in fat metabolism in mammals. In humans, having the ApoE4 variant reduces the average age of Alzheimer’s onset by several years compared with having the most common variant, ApoE3, while rarer ApoE2 appears to have a protective effect against this disease.
Using genetically modified mice that model Alzheimer’s disease and produce the human forms of ApoE4 and amyloid beta, the researchers from the University of Texas Southwestern Medical Center (UT) showed that the positive charges on ApoE4 caused this protein to clump inside early endosomes because the charge of ApoE4 matches that of the environment inside endosomes. This clumping prevents these organelles from continuing their journey through the cell to transport, recycle, or help dispose of other proteins, including amyloid beta.