ADHD, Alzheimer’s, and the “Paisa Mutation”

For generations, the “foolishness” has suddenly struck middle-age members of an extended family in Colombia’s Antioquia region.  It starts with mild forgetfulness but soon 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, concentrated by the intermarriage that’s not unusual in this rather isolated area. The malady is a type of early-onset Alzheimer’s Disease.

It’s called the “Paisa Mutation” because this clan of 5,000 are called Paisas. They are descended primarily from a group of 16th Century Spanish immigrants. 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 a recent story in The New York Times.

This isn’t the first time genetic discovery has taken place in the Paisa population. In fact, researchers studying this unique group of people 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).

What’s so special about the Paisas?  They are a so-called genetic isolate population. They have mixed very little, genetically speaking, with outside populations for generations.  As the population has increased, the gene pool has become “concentrated.”  Thus, they provide a rare opportunity to tease apart the link between genes and the human traits and 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, 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 genetic isolate that has long interested ADHD researchers, however, is Colombia’s Paisa people.

If you have a chance to attend a presentation by Max Muenke, M.D. on the genetic links to ADHD, please do so.  (I enjoyed such an opportunity at a CHADD conference several years ago.) Muenke is chief and senior investigator of the Medical Genetics Branch of the National Genome Research Institute; not only is he a very smart guy, he is also an engaging speaker with a knack for explaining these highly complex concepts in layperson’s terms. His team published the research mentioned above (on ADHD and conduct disorder).

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, including 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.

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