Man Found to Have a Rare Mutation That Prevents Alzheimer’s

Man Found to Have a Rare Mutation That Prevents Alzheimer's | The Lifesciences Magazine

An Alzheimer’s disease family history can seem like a dark, foreboding cloud to some people. However, there is a glimmer of hope emerging from the darkness: researchers have identified a second guy who should have displayed Alzheimer’s signs in his early 40s but did not.

The instance joins another that was previously discovered to have a genetic mutation believed to have contributed to the delay of symptoms of her own underlying Alzheimer’s disease.

The First Case

The previously reported Colombian guy didn’t get a life-changing diagnosis in his prime; instead, he continued working until he retired in his early 60s, and it wasn’t until he was 67 that the first signs of cognitive deterioration were apparent.

His brain had atrophied and was filled with the typical molecular signs of the disease, such as numerous sticky protein clumps called amyloid plaques and a small number of tangled knots of another protein called tau. People with severe dementia frequently exhibit these aggregates. However, the man had managed to fend off Alzheimer’s illness for a lot longer than anyone had anticipated.

It turns out that the man also had an uncommon variant in a different gene that codes for a protein called reelin, which seems to have prevented him from getting Alzheimer’s disease for more than two decades. These two genetic variants together predicted the man’s diagnosis.

The man had very low levels of twisted tau in a limited, focused area of his brain where neurons important in memory and navigation reside. In this one crucial area of the brain that typically succumbs to the disease relatively early, it was as if the genetic lottery had bestowed upon him a protective protein that kept Alzheimer’s disease at bay.

Although little is currently known about reelin’s function in Alzheimer’s disease, studies on animals conducted by a team of researchers led by Colombian neurologist Francisco Lopera demonstrated that the mutant form of reelin also prevented tau proteins from tying together around neurons in mouse brains. The team’s research was released in Nature Medicine.

Neuroscientist Catherine Kaczorowski told Nature that reading the report “made the hair on my arms stand up.” Catherine was not involved in the study.

“It’s just such an important new avenue to pursue new therapies for Alzheimer’s disease,” said Kaczorowski, a researcher at the University of Michigan in Ann Arbor.

New Findings

Researchers are hoping to learn more about how reelin interacts with Alzheimer’s proteins and defends neurons from their clutches in order to find a strategy to increase resilience in people with all types of Alzheimer’s disease, not only those who inherit its protective variation.

However, we are learning a lot about Alzheimer’s disease from families like the one Lopera has been observing in Colombia for almost 40 years. Many of the 6,000 members of the man’s extended family, which spans decades and generations, carry a mutation that makes Alzheimer’s first manifest in middle life.

It is frequently referred to as the Paisa mutation in honour of those in Colombia’s Antioquia area who have donated their bodies, brains, and blood to advance scientific understanding.

Alzheimer’s research, according to a 2019 article by journalist Jennie Erin Smith for Undark, “leans heavily on families with early-onset, genetic forms of the disease to understand its progress and test therapies that might interrupt it.”

In the most recent study, Lopera and colleagues at the University of Antioquia in Medelln, Colombia, examined clinical and genomic information from over 1,200 members of that Colombian kindred. The man who retained cognitive function and his sister, who had less protection than her brother and had passed several years previously, were both found to have the novel and highly unusual variety.

2019 saw the publication of another instance of a lady with the Paisa gene who did not exhibit any signs of cognitive deterioration until she was in her 70s, which is around 30 years later than what is typical for carriers of the mutation. She also had remarkably low tau levels throughout her brain, according to studies, but her resistance to Alzheimer’s was attributable to a distinct mutation in the APOE gene.

The protective impact of the variant reelin and APOE proteins is thought to be explained by some overlap or interaction between the two proteins, however it’s also likely that other genetic variants have a role. According to Lopera and colleagues, the results only serve to inform future theories regarding Alzheimer’s disease.

If reelin signalling pathway-targeting therapies were to be created in the future, they “may have a profound therapeutic impact on the resistance to tau pathology and neurodegeneration, and resilience against cognitive decline and dementia in Alzheimer’s disease,” the researchers write.

The study was released in Nature Medicine.

Also Read: Early Detection of Alzheimer’s possible through eye tests, reveals a study

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