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The largest known extended family in which several members face a high risk of developing early-onset Alzheimer's disease lives in Antioquia, Colombia. About 1,800 out of 5,000 family members carry a mutation in the gene PSEN1, predisposing them to the early-onset form of the disease called autosomal dominant Alzheimer's disease (ADAD).
In a study led by Massachusetts General Hospital, researchers worked with some members of this unique family to explore whether an emerging technology called tau PET (positron emission tomography) imaging can detect signs of Alzheimer's in the brain long before symptoms set in. Their findings could change how the disease is detected and treated.
What Tau PET Imaging Can Reveal
For many years, PET imaging was only useful for diagnosing Alzheimer's disease after death. The emergence of tau PET imaging has made it possible for clinicians to detect Alzheimer's-associated changes in the brain while patients are still alive. Tau PET scans show the accumulation of tau, a protein in the brain that contributes to breakdown of tissue that leads to memory loss. PET imaging can also detect beta-amyloid, another protein forms clumps in the brain and contributes to declining cognitive abilities.
A Mass General research team that included Yakeel T. Quiroz, PhD, director of the Familial Dementia Neuroimaging Laboratory, and Keith A. Johnson, MD, associate radiologist and director of Molecular Neuroimaging, recruited 24 members of the Colombian family for the study. They used PET imaging to search for deposits of tau and beta-amyloid in their brains.
Drs. Quiroz and Johnson found that half of the 24 family members carried the PSEN1 mutation, and nine of those carriers had not yet developed cognitive impairments. Their mean age was 38.
Predicting a Problem
The diversity of the study subjects' results allowed the researchers to draw clear lines between the PSEN1 mutation and deposits of tau and beta-amyloid.
The Mass General researchers discovered that deposits of beta-amyloid were present in the nine PSEN1 mutation carriers' brains about 15 years before the predicted onset of mild memory loss. Elevated levels of tau could be seen six years before symptoms were expected to emerge. A significant accumulation of tau was only evident in the three mutation carriers who were already showing symptoms and in one of the 12 participants who wasn't.
The researchers asked the study participants to take memory tests along with a questionnaire used to measure cognitive impairment. They reported that higher levels of tau corresponded closely with poor performance on those tests.
The Future of Alzheimer's Treatment
The researchers believe they were the first to use PET images to track the buildup of tau. Their results could boost ongoing efforts to determine whether treating patients before they develop symptoms can slow the progression of Alzheimer's.
There are already studies underway to do just that. One trial, for example, involves 252 members of the Colombian family group who face a high risk of developing the disease. The participants will either receive a placebo or the experimental drug crenezumab, which is designed to prevent the buildup of beta-amyloid deposits in the brain.
Dr. Quiroz and her colleagues noted that larger studies are needed to determine the usefulness of tau PET in late-onset Alzheimer's or forms of the disease that may be caused by other genetic mutations. Still, the research team wrote that the findings from this study provide compelling evidence that tau PET imaging could prove to be a useful biomarker to identify high-risk indifviduals for Alzheimer's and track the progression of the disease.
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