Early Immunotherapy Clears Alzheimer's Plaques

Researchers have found that antibodies specific for Ab peptide, the basic element of the amyloid-beta plaques found in the brains of victims of Alzheimer's disease, can be used to clear the brain of both amyloid plaques and tau neurofibrillary tangles as long as the treatment is begun early in the course of the disease.

Investigators at the University of California, Irvine (USA) used a triple transgenic mouse model (3xTg-AD) that develops both amyloid plaques and tau tangles in Alzheimer's disease-relevant brain regions. These animals were treated with antibodies specific for Ab peptide.

Results published in the August 5, 2004, issue of Neuron revealed that this immunotherapeutic approach reduced not only extracellular amyloid plaques but also intracellular amyloid accumulation and most notably led to the clearance of early tau tangles. Amyloid deposits were cleared first, and if treatment was suspended, subsequently reemerged prior to the tau tangles. Hyperphosphorylated tau tangles, which are characteristic of advanced Alzheimer's disease, were resistant to clearance.

The authors said, "Taken together, these data provide compelling evidence for the amyloid cascade hypothesis that Ab lies upstream of tau in the neurodegenerative cascade leading to Alzheimer's disease and further suggest that Ab-based therapeutic approaches may be efficacious in removing both hallmark lesions. The most clinically relevant finding is that using anti-Ab-based therapeutic approaches can clear the tau burden. However, since tau becomes resistant once the protein becomes hyperphosphorylated, administering immunotherapy late during the disease may still clear amyloid plaque, although it will be insufficient to impact the neurofibrillary pathology.”




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University of California, Irvine