Each and every one of us at some point in our lives has faced memory loss. Fleeting, maybe. More worrisome as we grow older. It’s not about waking up in the morning and not knowing where you are, or the proverbial “Where have I placed my keys?” As a pathological deterioration of brain cells, Alzheimer’s erases your memory. You forget your name. You forget how to dress. You forget the faces and tender words of loved ones.
In central Antioquia, across small towns such as Angostura, La Carolina and Yarumal, Alzheimer’s disease strikes early. Many young men and women in their thirties show progressive signs of memory loss. Sometimes the early onset of the disease is combined with other neurological disorders such as Parkinson’s, epilepsy and schizophrenia. For many decades these individuals were shut off from society, hidden from public view and more tragically, thrown out on the street. For those who couldn’t explain sudden memory loss, they referred to it simply as “La Bobera”- the stupidity.
Dr. Francisco Lopera Restrepo, Professor and Head of the University of Antioquia’s Clinical Neurology Department has been in close contact with Alzheimer’s disease since he was a young man growing up in La Aurora, a small town near the epicenter of early-onset Alzheimer’s. Surrounded by close family and school friends who acquired the disease later on in life, Lopera became fascinated with how the brain works and decided to study Medicine with a specialization in Behavioral Neurology at his alma mater in 1970.
The mysterious relationship between the brain and how the mind processes or loses memory is at the core of Dr.Lopera’s historic research. “The brain is the hardware, while the mind is our software,” explains Dr.Lopera as we meet at the laboratory of the Investigations Centre of the University (SIU) where all his research is conducted and housed.
Dr.Lopera’s investigations into early-onset Alzheimer’s date back to 1984 when he met his first family with the disease. Working towards his PhD he started looking into the genealogy of the family, realizing that the gene mutation went back generations. “It was hereditary and always began early,” recounts Dr.Lopera. As a first contact with a specific family-inherited disease, the researcher came across a similar case in the town of Yarumal. Here, a young man who sold lottery tickets had also lost his memory. So had his father and grandfather before him. Even some of the young man’s extended relatives.
A third case then turned up. This time it was a young woman from the town of Angostura in the central Andes. Although they all seemed to belong to different families spread across the mountainous Antioquia territory, Dr.Lopera began mapping the gene mutation of Alzheimer’s as it spread, devastating entire families and leaving few clues, and he was able to identify 25 different families with the exact same story.
Investigating birth certificates in parishes and going to public notaries, Dr.Lopera found that 14 of the 25 families came from the same genetic “trunk” and that this strand of Alzheimer’s moved from branch to twig relatively undetected. “I am convinced now that all 25 families are connected,” states Lopera.
The scientist has traced the gene back to the 1740s. Prior to this date, the gene could have originated in Spain or mutated locally. What is clear is that the gene has a “founding factor.” The Alzheimer’s gene known as the mutación paisa or Paisa mutation (Paisa being the name given to the inhabitants of Antioquia and its capital, Medellín) has three stages of development. First is a pre-clinical phase when the gene strikes without the host knowing. There are no symptoms, no outward manifestations of memory loss. Then, a secondary stage when memory starts failing without cognitive breakdown. The third and final stage is brain atrophy or dementia.
“Before we only spoke of Alzheimer’s when the patient had dementia,” states Lopera. “Thanks to these families we have been able to clearly define the three stages.” For the family clans beset with early-onset Alzheimer’s, the first stage starts between the ages of 28 and 30. To reach this important medical marker, Dr.Lopera took 50 candidates to the Banner Alzheimer’s Institute in Phoenix, Arizona, to have PET scans of amyloid plaque build up. Amyloid-beta is a protein in the brain of patients with the disease.
Of the 50 volunteers, 20 were gene carriers, 20 were gene clean and 10 already showed early signs of clinical Alzheimer’s. None of the 40 pre-symptomatic candidates knew of their status with the disease or how it might develop. One medical fact was very evident: every person who carries the ‘Paisa mutation’ will inevitably get sick and develop Alzheimer’s.
After the first undetectable stage was deciphered, Dr.Lopera marked his second phase of cognitive impairment at age 44. Full dementia at age 49. Mapping the gene across 5,000 members of Antioquia as well as finding the “markers” for the developmental stages of the disease has catapulted Dr.Lopera to the top of medical research into Alzheimer’s. He has been extensively profiled in leading medical journals such as The Lancet and periodicals, such as The New York Times, and invited to join a global team of researchers who this year will begin work on a clinical trial that could eventually lead to a treatment and a drug called Crenezumab (created by Genentech) to stop the gene from developing into all out disease.
The Alzheimer’s trials in which Dr.Lopera’s early-onset Antioquia research is fundamental will span five years and cost USD $100 million. In as much as it represents a historic moment for medical research into one of the world’s most feared diseases, whatever the outcome may yield, the investigations could offer relief to millions around the world who suffer from conventional Alzheimer’s.