Could One Family Hold the Key to Curing Alzheimer’s?
At the age of 82, Laura Cuartas is watching her four children deteriorate in front of her eyes. Starting around the age of 45, they developed what she describes as “the most terrifying illness of the world”, Alzheimer’s disease (AD). This early onset of the disease is due to a genetic mutation and it progresses rapidly. Within a few years after symptoms arise, around the age of 45, almost all sensation and function is gone. At age 61, Cuarta’s daughter Maria Elsy, is mute and fed by a nose tube. Her son, Dario, is 55 and babbles incoherently. Laura Cuarta is not the only parent who must take care of her children as they fall victim to this disease. In Antioquia, Colombia, she is a part of the largest known extended family to have this familial Alzheimer’s disease. Of the 5,000 members, about a third of them have the presenilin-1 dominant genetic mutation, guaranteeing they will get the disease.
Familial Alzheimer’s only accounts for about 10% of cases of AD. Most cases come from a genetic mutation at presenilin-1, presenilin-2 or the APP gene. Mutations to these genes almost guarantee that an individual will get the disease. For many years, this extended family’s strain of the disease was thought to be isolated, giving us no information about the Alzheimer’s most of us are familiar with- Sporadic Alzheimer’s Disease. This form has an onset of 65 years old. Other than age and family history, there has been no solid risk factor to explain why more than five million American’s are suffering. The APO4 gene has found to be a risk gene, meaning that mutations to this will increase your chances of developing AD, but the disease is not guaranteed. While Sporadic and Familial Alzheimer’s may have different causes, they both result in the same brain changes and symptoms. Plaques and tangles occur in the brain, along with a reduction of synaptic density and neuronal loss.
This is where the Colombian family comes in. Many neuroscientists believe that they are our best hope at unlocking this mysterious disease. Through genetic testing, scientists know exactly who will get the disease. In a 2010 study, using a face to name matching test twenty carriers of the genetic mutation and nineteen non-carriers from this extended family were used to examine hippocampal function years before the onset of clinical symptoms. The hippocampus, a big component of our memory system, is a major part of the brain that is damaged due to Alzheimer’s. Presymptomatic carriers showed greater right anterior hippocampal activation than the matched controls, even twelve years before the average age of onset of the disease. This increased activity could be the brain’s way of compensating to maintain normal cognition. These results could also be because of excitotoxicity due to a disruption of calcium homeostasis. In a study done in 2013, the same population was tested to see if cortical atrophy could also be found before the display of clinical symptoms. It was found that cognitively normal carriers had a thinner cerebral cortex than non-carriers in regions affected by typical sporadic AD, specifically the precuneus, superior parietal lobule, and the angular gyrus.
These presymptomatic changes could act as a preclinical biomarker not only for familial, but sporadic Alzheimer’s disease. These results show that at least six years before the onset of AD, patient’s brains have already begun going through significant changes. Our current approach of treatment once symptoms arise may be too late. By targeting these early changes, there may be a way to delay the onset or even stop the progression of the disease. That is the goal for the new Gentech drug, Crenezumab, which targets beta amyloids and stops them from becoming toxic. This trial is the first to Alzheimer’s drug to be tested on seemingly healthy people, specifically the family in Colombia. One hundred carriers will take the drug and one hundred will take a placebo for five years. An additional hundred non-carriers will also take it. Similar branch studies are also being run across the US. The Gentech trial will prove whether or not amyloids are the root of Alzheimer’s and the brain changes that come with it.
There are currently over five million Americans (that’s about 1 in every 9) suffering from Alzheimer’s. The cost of care and treatment is more than $200 million. But with every study completed and trial run, we are steps closer to finding the root of this disease and possibly a cure.
Hippocampal Hyperactivation in Presymptomatic Familial Alzheimer’s Disease – Quiroz: American Neurological Association
Genetic Studies in Alzheimer’s Disease – Tang
Cortical Atrophy in Presymptomatic Alzheimer’s disease presenilin-1 mutation carriers – Quiroz: Journal of Neurology, Neurosurgery, and Psychiatry
Alzheimer’s Stalks an Extended Colombian Family – Belluck: NY Times
Alzheimer’s Plagued Colombian region is focus of drug trial – Kraul: LA Times