Man who defied genetics for decades may hold a clue to preventing Alzheimer's, scientists say

CNN

Researchers who are trying to uncover the secrets of Alzheimer’s disease have been given an important clue that may help protect those at risk of this type of dementia.

According to family history, a man who was destined to suffer memory loss by his 50s or 40s, maintained normal function decades longer than expected. A rare gene mutation that increased the function of a neurotransmitter protein may have protected him.

Scientists believe that understanding the way this gene change protected his brain could help other people prevent Alzheimer's.

The man belongs to a large Colombian family, where many of its members have inherited the mutated presenilin-1 gene, or PSEN1. PSEN1 carriers are more likely to develop Alzheimer's at an early age.

The man with the PSEN1 mutation did develop memory and cognitive problems. At 72 years old, he was diagnosed with mild Alzheimer's disease. He then suffered from memory loss and an infection. He died from pneumonia at the age of 74.

He should have been experiencing memory and cognitive problems for decades. Doctors found beta amyloid, tau and other proteins in his brain. These are the same proteins that build up in Alzheimer's patients.

He also had another thing working for him. Genetic analysis revealed the man's rare mutation in a gene which codes for reelin, a protein that helps nerve cells to communicate.

In this case, Dr. Joseph ArboledaVelasquez is an associate professor at Harvard University, and the lead author of a study about this man.

He said, 'This gives us an enormous insight.' It is very clear that putting more reelin into the brain could actually help patients.

The study was published in Nature Medicine on Monday.

The improved reelin protein appeared to protect a very specific area of the man's head, an area behind the nose and at the base of his brain called the Entorhinal Cortex.

Arboleda Velasquez stated that a big insight gained from this case was the fact that you may not need to have this in every part of your brain.

The entorhinal cortex is especially sensitive to Alzheimer's and aging. This area of the mind also transmits and receives smell-related signals. The loss of smell can be a sign of brain changes leading to memory and cognitive difficulties.

Arboleda Velasquez explained that Alzheimer's disease starts in the entorhinal cortex and then spreads.

It is the second instance that Arboleda and her team have discovered someone who has defied the genetic odds.

Scientists reported a case in 2019 of a woman, who was expected to develop early Alzheimer's disease but maintained her memory and cognitive abilities into her 70s.

She had two copies of a mutation in her APOE3 that was dubbed the Christchurch mutation. The APOE3 activity was reduced. APOE, like reelin is a signaling molecule known to influence a person's Alzheimer's risk.

It turns out there's a connection between the two: the receptors found on cells that are responsible for reelin, are also receptors for APOE.

They are like two big arrows. They are telling us: "Hey, this is the path." "This is the path that is essential for extreme protection from Alzheimer's," Arboleda Velasquez said.

The pathway is not protective for all. It was not as beneficial for the sister of the man who participated in the study, although she also had the rare protective gene mutation. Her family reported that she started experiencing cognitive decline around age 58.

Arboleda Velasquez explained that this could be because the activity of the gene in women seems to decrease with age. Therefore, it does not produce as much reelin. He said that women can have the variant but don't show it as much as males.

Harvard's team has already begun developing a treatment based on their findings.

Dr. Richard Isaacson is a preventive neurologist at Florida Atlantic University. He says that studies like these show us an important thing: 'In some cases, we can beat our genes.

Is this a sign that a cure may be on the horizon? It remains to be determined.

Can we use this study to improve and transform the care system? I hope so. Isaacson, a researcher who wasn't involved in this study, said, "I wouldn't say we're there yet." "But I believe this is a very important study."