Could studying a genetically linked population shed light on a link between ADHD and Alzheimer’s Disease? That is just one of the questions researchers are pondering.
For generations, a disease called the “foolishness” has suddenly struck middle-age members of an extended family in Colombia’s Antioquia region. It starts with mild forgetfulness. Soon, however, it reduces its victims to infantile incapacitation.
People here have long attributed La Bobera to a host of superstitions: a mythic priest’s revenge or touching a mysterious tree. Scientists now know it is a genetic mutation. The mutation has been concentrated by the relatively high rates of intermarriage. Until the 19th Century, this population in this mountainous remained rather isolated.
The malady is a type of early-onset Alzheimer’s Disease. It’s called the “Paisa Mutation”.
Population Descended From A Few Spanish Families
Broadly speaking, Paisa is the name for people from Colombia’s northwest corner of Columbia. They are descended primarily from a group of 16th Century Spanish immigrants.
A mutation occurs when DNA is damaged or changed in such a way as to alter its genetic message; that message is then passed down through the generations. (More about mutations here.)
By studying this mutation, researchers hope to learn more about other forms of Alzheimer’s and its treatment. Pam Belluck shares the dramatic details on the disease and its discovery, along with hopes for treatment, in The New York Times. (There is an article, “Alzheimer’s Stalks a Columbian Family“, and a video, “The Vanishing Mind”)
This isn’t the first time that genetic discovery has taken place in the Paisa population. In fact, researchers studying this unique population have learned much about ADHD from them, too. For example, a genetic link between ADHD and conduct disorder/oppositional defiance disorder was discovered by studying selected Paisa families (multi-generational).
“Genetic Isolate” Populations Reveal Heritable Traits
What’s so special about the Paisa? They are a so-called genetic isolate population. For generations, they have mixed very little, genetically speaking, with outside populations. As the population has increased, the gene pool has thus become “concentrated.” Thus, they provide a rare opportunity to tease apart the link between genes and the human traits/diseases the population experiences at greater-than-average rates.
Ethnic Finns are considered a human genetic isolate (to read about the 40 rare hereditary diseases more prevalent in Finland than anywhere else in the world, click here). So are the inhabitants of Tristan da Cunha, pictured above, a remote island in the south Atlantic Ocean settled by British Marines in the early 1800s. Their population is beset by asthma in greater-than-average numbers.
The Paisa and ADHD: Genetic Research
The genetic isolate that has long interested ADHD researchers, however, is Colombia’s Paisa people.
Several years ago, I enjoyed a presentation by Max Muenke, M.D. on the genetic links to ADHD. Muenke is chief and senior investigator of the Medical Genetics Branch of the National Genome Research Institute. His team published the research mentioned above (on ADHD and conduct disorder). Below is a figure from another study: “Attention-deficit/hyperactivity disorder (ADHD): Feasibility of linkage analysis in a genetic isolate using extended and multigenerational pedigrees“.
More recently, the research team discovered that certain variants in one gene (LPHN3) act as a trigger for ADHD. They did this by first analyzing data from their studies of the Paisa families. Then they validated their findings by replicating the study in samples from other populations. That included two in the U.S., indicating that the mutation is not likely to be a statistical curiosity restricted to the Paisas. (Perhaps your family participated in the research.) You can read a report about the study here.
Is there a link between the “Paisa Mutation” and the higher-than-average prevalence of ADHD among the Paisas? That has yet to be explored. Stay tuned.
Meanwhile, here is a presentation from Dr. Muenke:
I welcome your comments; no registration required.
If you enjoyed this post, please subscribe and share with others via the handy links below.