Some people have the misfortune of experiencing a rare mutation in a gene called presenelin 1, which causes early memory loss.
Presenelin 1 triggers memory loss in people as young as 40 and develops into full blown Alzheimer’s by the late 40s, inflicting death by age 60, or thereabouts.
Scientists discovered the group of people hardest hit by this memory-robbing gene mutation is an extended family living in the Medellin area of Columbia. Over the centuries, scientists estimate more than a thousand members have been struck down by this cruel mutation.
All, that is, except one.
This woman, now in her 70s, has the mutation yet remains dementia free. Here’s her remarkable story.
For decades Dr. Franciso Lopera, a Colombian neurologist, together with a group of U.S. scientists, have been interested in the large number of family members in Medellin with early onset Alzheimer’s.
Gathering family records and building a brain bank of those who developed the disease, Dr. Lopera helped discover the presenelin 1 mutation.
Then he came across a woman who had the mutation, yet only developed mild cognitive impairment in her 70s.
This seemed impossible. She should have died from Alzheimer’s years ago. So, Dr. Lopera put her on a plane bound for the Massachusetts General Hospital, Boston, where other member of the research group worked with Dr. Yakeel Quiroz.
Amyloid Through the Roof, Yet No Dementia
Dr. Quiroz and his team used brain imaging to examine her brain. They found amyloid plaques, considered the hallmark of Alzheimer’s, all over her brain tissue. In fact, they were “[t]he highest levels of amyloid that we have seen so far,” said a surprised Dr. Quiroz.
Despite the amyloid plaque, other markers of Alzheimer’s — toxic tau tangles, neurodegeneration, brain atrophy — were largely absent.
What was going on?
Dr. Quiroz contacted a Harvard cellular biologist, Dr. Joseph Arboleda-Velasquez, to conduct further research.
Extremely Rare Mutation Provides the Key
After extensive testing, Dr. Arboleda-Velasquez discovered this woman has a second, extremely rare mutation of the APOE gene.
Variations of this gene — APOE2, APOE3 and APOE4 — are well known to increase the risk of Alzheimer’s, but the Colombian woman had, in addition to presenelin 1, two copies of APOE3, and both of these had a mutation called APOE3Christchurch (APOEch)– named after the city in New Zealand where it was first identified.
Dr. Arboleda-Velasquez knew that having one APOEch mutation does not stop the development of early Alzheimer’s in those with presenelin 1, so he theorized the second mutation was the key. It “really kind of sealed the deal,” as Dr. Arboleda-Velasquez put it.
What seems to be happening, although not conclusively proven, is that APOEch prevents presenelin 1 from binding to certain sugar molecules that coat neurons. This makes it very hard for tau proteins to spread between cells. So, while amyloid growth goes unabated, tau tangles are prevented.
Dr. Arboleda-Velasquez’s remarkable discovery adds to the growing number of studies that cast doubt on the role of amyloid in the formation of Alzheimer’s disease. As readers of this newsletter already know, I think the weight of evidence is against the amyloid theory. This case provides dramatic new evidence.
Dr. Yadong Huang from Gladstone Institute of Neurological Disease, San Francisco, wrote a commentary about the case. This was published alongside the original article in the journal Nature Medicine in November.
Dr. Hang wrote “it actually illustrates, to my knowledge for the first time, a very clear dissociation of amyloid accumulation from tau pathology, neurodegeneration and even cognitive decline.”
Experts Line Up in Praise
Dr. Quiroz said, “This single case opens a new door for treatments of Alzheimer’s disease … promoting resistance even in the face of significant brain pathology.”
And Dr. Arboleda-Velasquez added, “What this patient is teaching is there could be a pathway for correcting the disease.”
Dr. Lopera is just as excited by the research. In his view, “This case is a big window to discover new approaches.”
Even experts not involved with the study were impressed.
Fiona Carragher, chief policy and research officer at the Alzheimer’s Society UK believes this case study is a turning point: “This is a rare example where the study of just one person could change the thinking of a whole research field.
“This breakthrough opens up a new and promising avenue of Alzheimer’s research. The hope is that this exciting scientific advance could lead to new treatments and take us a step closer towards a cure.”
Dr. Guojun Bu, chair of the neuroscience department at the Mayo Clinic, and an APOE researcher to boot, believes the implications could be profound.
“When you have delayed onset of Alzheimer’s by three decades, you say WOW.”
This is exciting research indeed. Hopefully, this gene mutation discovery will lead to a real advance in the treatment of Alzheimer’s. Right now, conventional medicine doesn’t offer much to patients suffering from Alzheimer’s related memory decline.
It’s important for me to add that I believe Alzheimer’s disease is much like cancer, meaning there’s not just one cause, or one cure. Whether you have a genetic predisposition to Alzheimer’s disease or not, you can make important lifestyle choices to help prevent memory loss from ever developing, and to slow it down dramatically if it does.
Some lifestyle choices that I recommend and follow myself include a healthy diet, regular exercise for your body and your brain as well as a nutritional supplement regimen that supports brain health.
