Antibodies Fight Alzheimer's

Immune therapy for alzheimer's disease--and the amyloid cascade theory on which it's based--received a boost last week from research published in Neuron [43, 321 (2004)].

Most Alzheimer's patients' brains contain plaques made of amyloid-ß peptide (Aß) as well as neurofibrillary tangles consisting of tau protein. The amyloid cascade hypothesis holds that the plaques form first, they lead to the formation of neurofibrillary tangles, and both act to kill off nerve cells in the brain. Immune therapy utilizing antibodies to Aß is being studied as a means to rid the brain of this peptide and ward off the disease.

Now, researchers at the University of California, Irvine (UCI), have employed immunotherapy to demonstrate "for the first time that clearance of amyloid also results in the removal of early-stage tau pathology in mice," according to a commentary in Neuron by neuroscientists Michael L. Hutton and Eileen M. McGowan of Mayo Clinic College of Medicine, Jacksonville, Fla. "These findings provide compelling evidence that pathological Aß species induce the progressive accumulation of tau in ... neurons, eventually resulting in neurofibrillary tangle formation."

UCI neurobiologist Frank M. LaFerla, doctoral student Salvatore Oddo, and their colleagues treated one-year-old mice with a single injection of anti-Aß antibodies. Within three days, the treatment had cleared Aß deposits in the section of the brain where the injection occurred. A couple of days later, the number of tau lesions had also declined. After a month, however, Aß deposits reemerged, and tau pathology redeveloped some days later.

The UCI team notes that clearance of tau depends on its state. As Alzheimer's disease progresses and tau becomes more phosphorylated, the treatment is less able to clear tau aggregates.