One woman’s latter life was practically prewritten. Her early-onset Alzheimer’s dementia was predicted to manifest in her 40s or 50s due to various gene mutations that predisposed her to the condition. Scientists are interested in discovering why Colombian Aliria Rosa Piedrahita de Villegas, who was free of neurological disease until her 70s, instead enjoyed a healthy life.
We know very little about the complicated past of Alzheimer’s disease (AD). Some cases, according to scientists, are brought on by an accumulation of a protein called -amyloid that is misfolded and causes neurotoxicity. The emphasis of current AD therapy is preventing these plaques.
Treatments aimed at this notion have been available for a while; they appear to have great success in animal models but consistently fall short in human trials. Scientists have been perplexed by this discrepancy, which also raises new concerns about the original amyloid hypothesis. Some have even argued that AD isn’t even a brain illness.
This takes us to the woman in question, who although having all the symptoms of early-onset AD, nonetheless manages to avoid them. Watching this woman’s death from cancer, researchers gathered her remains for an autopsy in an effort to pinpoint exactly what was maintaining her brain health. They had been following her throughout her life.
She has two mutations in the gene APOE3, often known as the Christchurch mutation, and a mutation in the risk gene PSEN1. Variants of PSEN1 are present in 70% of cases of early-onset AD, and APOE3 is one of the main risk genes. These mutations are strongly associated with the development of AD and increase the risk in a number of ways.
Amyloid plaques developed as expected as a result of the PSEN1 mutation, however they functioned differently in this instance. Amyloid plaques often develop clusters around crucial brain areas involved in memory and cognitive processing, however they didn’t in Aliria’s brain.
Instead, her occipital brain, which is involved in visual processing, had a greater quantity of tau tangles (another characteristic of AD), and her overall disease development was different from that of other PSEN1 carriers.
Therefore, how did she manage to avoid AD for so long? Though they are still unsure, the scientists think it has to connection with the Christchurch mutations. Being Patient was informed that this was the only hereditary characteristic they could attribute the resilience to. They discovered that altering the APOE3 gene similarly in animal cells affected how tau tangles were distributed and slowed the disease’s progression.
Now, they are hoping that this exceptional brain can contribute to the development of novel therapies for AD, which continues to be one of the biggest medical issues of our time.
