In this week’s issue of the journal Nature, Dr. Sam Gandy – a highly regarded Alzheimer’s expert from Mount Sinai Medical Center – argues that the past century of scientific research on the memory-impairing condition indicates that, “Prevention is better than cure.”
To Recap
- In 1907, Alois Alzheimer published the description of a 55 year-old woman who had slowly lost all cognitive function before an untimely death. Because of the relatively young age of the patient, the disease became regarded as an uncommon mid-life disease.
- In 1970, neuro-patholigists realized that ‘senile dementia’ was indistinguishable from what Alzheimer had described. The buildup of amyloid plaques and the associated tangles within the neurons was then renamed Alzheimer’s disease.
- The definition of ‘senile dementia’ was also broadened to include the disease that we now consider the major cause of dementia.
- In the late 1980s, researchers identify the major plaque protein as the amyloid-β peptide.
- In the 1990s, researchers identify three genes that collectively contribute to the buildup of amyloid-β. However, mutations in these genes only accounted for about 3% of Alzheimer’s disease.
- In this same era, transgenic mice were developed to study the effects of amyloid plaques in the brain and to identify possible vaccines.
- In 2001, the first vaccines were developed and human trials began. However, initial trials were of little use because they included no method for measuring how much amyloid-β was in the brain.
- In 2004, the challenge of measuring the amyloid plaque buildup was overcome with the use of PET scan technology.
- In 2010, researchers from the University of Turku in Finland showed that immunotherapy could lower plaque burden by up to 25%. Yet the decrease in plaque burden failed to amount to any measurable improvement in cognitive function. This is where we stand today.
Gandy argues that there are several explanations for the discrepancy between “perceived cause” and “observable benefits.” First, it could be that the 1.5 years of immunotherapy (standard in initial trials) or the 25% reduction in plaque burden is insufficient to produce the desired results. Researchers are exploring this possibility and results are expected by 2013.
Another possibility is that the antibody used may not recognize the most neurotoxic conformations of amyloid-β. Dozens of different antibodies are now in clinical trials and results are expected in the years to come.
Yet another possibility is that by the time the symptoms of Alzheimer’s disease are observably present, the damage to the brain is already irreversible. This is because the biomarkers associated with Alzheimer’s disease are present in the brain 10-20 years before symptoms become noticeable. Therefore, starting therapy upon onset may be like attempting to fix something that is already beyond repair.
Gandy concludes by suggesting, “The amyloid-β odyssey of the past 25 years has shown that conquering Alzheimer’s disease is not a matter of removing amyloid-β plaques from the brain post hoc… [Instead,] Perfecting the selection of subjects and the timing of intervention could delay the onset of Alzheimer’s disease… [Therefore, preventative] intervention to lower amyloid-β levels is now the best hope.”
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