Alzheimer, a rare mutation has prevented a man from falling ill – breaking latest news

His life seemed marked: he should have developed an early form of Alzheimer’s by the age of 40 due to a genetic variant call Presenilla 1 which causes autosomal dominant Alzheimer’s disease, leading to death by age 60 from complications of dementia. Instead this Colombian man, mechanic, father of two children, continued to work until he retired shortly after his 60th birthday. StOnly at 67 did the first signs of moderate cognitive decline appear
and the mechanic died in 2019 at the age of 74. This man is only the second patient identified with this miraculous ability to defy the devastating Alzheimer’s gene. Doctors now hope that these two cases will open up new avenues for therapy in able to prevent, or at least limitl’accumulation of tau protein in the brain e protect other people with Alzheimer’s disease.

Brain scans showed that this patient’s brain had atrophied, with beta amyloid plaques and tangles of tau protein typical of people suffering from severe dementia. Yet this man has resisted Alzheimer’s much longer than anyone expected.

What protected him

To protect him in genetics lottery been one second mutationa genetic variant of the gene Reln, already known to encode the reelin protein related to over twenty years of resistance to the hereditary form of Alzheimer’s that had affected humans. In this way managed to keep the disease at bay for a long time. The story of this lucky patient was featured on Nature Medicine where scientists from the Faculty of Medicine of the University of Antioquia in Medellin, Colombia, in collaboration with other European colleagues, underlined how the genetic mutation have protected a small portion of the patient’s brain, the corteccia entorinalewhich is essential for the memory. Precisely in that area the man had very low levels of tau protein.

Family studies

For decades, the neurologist Francisco Lopera of the University of Antioquia in Medelln, Colombia, takes care of and follows a extended familymany of whose members are carriers of the mutation tragically unfortunate, Presenillin 1. The rare mutation and its effects are aggressive and predictable. In general, people who carry this mutation begin to have a important accumulation of amyloid plaques already at twenty years of age. At age 30, accumulations of another Alzheimer’s-associated protein, tau protein, appear. People who carry this gene begin to suffer from first cognitive disturbances around the age of 44 and before the age of 50 they receive a diagnosis of full-blown dementia. They usually die around age 60. In total, scientists have found that 1,200 people out of an extended family of over 6,000 they carried this genetic time bomb. There is nothing that can be done to stop the progression of the disease.

The other patient

In 2019 researchers discovered another patient capable of defending itself against the same fate. This woman’s memory only began to wane at the age of 70. Her A to protect her for another genetic mutation dubbed Christchurch: although her brain was clogged with amyloid plaques she was relatively free of tau protein.

Experiments on mice

At present, little is known about the role of the gene Reln in protection from Alzheimer’s. Experiments on mice genetically modified to graft the mutation in the Reln gene conducted by a team of researchers led by the Colombian neurologist Francisco Lopera have shown that the mutation triggered a chemical change in the tau protein
such as to prevent it from accumulating on the neurons of mice.

The researchers studying the two cases found an overlap between the two different genetic mutations that helped protect the two patients: Both mutations affect proteins that bind to the same receptors on the surface of brain cells. Understanding the possible biochemical pathways that led to protection opens up new approaches for the drug development against the pathology which in Italy alone has over 500,000 patients.