Mayo Clinic Jacksonville researchers report evidence to suggest that prevention of amyloid beta (Abeta) deposition in the brain prior to Alzheimer's disease (AD) onset may be easier than curing established disease. An immunization strategy targeting Abeta42, or a second form of Abeta known as Abeta40, prevented onset of amyloid deposition in young, AD-prone mice. However, this strategy was not effective in altering Abeta deposition or clearance in mice with modest levels of preexisting Abeta deposits.
Current hypotheses suggest that it is the accumulation over time of amyloid beta peptide 1–42 (Abeta42) that triggers changes in the brain that lead to cognitive dysfunction in Alzheimer's disease. The reduction of amyloid levels is therefore a major therapeutic objective. Todd Golde and colleagues from the Mayo Clinic Jacksonville report evidence to suggest that prevention of amyloid deposition may be easier than curing established Alzheimer's disease. Their results will appear online on December 8 in advance of print publication in the January 2006 issue of the Journal of Clinical Investigation.
The authors use transgenic mice genetically predisposed to accumulate amyloid deposits in their brain to show that an immunization strategy targeting Abeta42, or a second form of Abeta known as Abeta40, prevents the onset of amyloid deposition in these mice at a young age. In contrast, the anti-Abeta42 or anti-Abeta40 monoclonal antibodies were not effective in altering Abeta deposition in mice with modest levels of preexisting Abeta deposits, nor were they capable of clearing existing deposits.
The results suggest that it may be easier to prevent Abeta deposition than to alter Abeta once deposited. This method may be an effective strategy to prevent amyloid deposition prior to the onset of Alzheimer's disease, but may have limited benefit in a therapeutic setting where amyloid deposits are already well established within the brain.
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
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