HudsonAlpha Research Report 2021-2022

UNRAVELING THE HIGH INCIDENCE OF

G lobally, Alzheimer’s disease and other dementias affect about 55 million people, with nearly 10 million new cases diagnosed yearly. This number is predicted to double every 20 years, reaching 139 million by 2050, making the need for preventative measures and better diagnostic tools critical. Studies show that significant damage to the brain has already occurred by the time individuals show signs of dementia. As such, available treatments show little benefit for individuals already impaired with dementia. Preventative dementia research is complicated by the difficulty of finding the appropriate participant base. Participants should be people guaranteed, or highly likely, to develop dementia — a population that is hard to identify because the cause of most common types of Alzheimer’s disease is largely unknown. A rare subtype of Alzheimer’s disease, called autosomal dominant Alzheimer’s disease (ADAD), presents a unique opportunity for researchers because several genetic causes are identified for the dis- ease, and mutation carriers always develop the disease at roughly the same age range. One family in Antioquia, Colombia, with a long history of ADAD, became a key cohort for Alzheimer’s disease research, serving as the subject of dozens of studies and one clinical trial. The dementia field is learning a lot about the cause and progression of this devastating disease from this family. In return, they received an answer to their decades-long question about why so many family members were suffering from, and ultimately dying from, this devastating disease. HudsonAlpha faculty investiga- tors Rick Myers, PhD, and Nick Cochran, PhD , are part

of the ongoing efforts to understand the dynamics of dementia by studying families in Latin America overburdened by the disease.

HOW A COLOMBIAN FAMILY FOUND ANSWERS WHILE GIVING BACK TO ALZHEIMER’S DISEASE RESEARCH Several decades ago, a neurologist named Francisco Lopera began studying the family in Antioquia because of their high incidence of very early onset Alzheimer’s disease. On average, the disease strikes individuals in this family in their mid-40s and results in death within 10 to 12 years. To date, more than 6,000 individuals from 26 extended families are enrolled in the study. By analyzing the individuals’ genomes, researchers discovered that many carry a rare genetic mutation for early-onset Alzheimer’s disease in a gene called Presenilin-1 (PSEN1) 1 . The mutation is referred to as PSEN1 E280A after the mutation’s location on the gene. Other Colombian families, unrelated to the Antioquia family, were also found to have high incidences of ear- ly-onset Alzheimer’s disease. Many of these families were from small, isolated towns like Antioquia. Small towns and villages in rural Colombia are often genetically isolated, meaning there is little genetic diversity because of a lack of immigration into the area. This creates the perfect environment for amplifying rare mutations, like the PSEN1 mutation. A recent publication confirmed the role of ances- try and genetic isolation in the mutational landscape of dementia in Colombia 2 . A group of researchers, including Drs. Cochran and Myers, analyzed the genomes of 900

HUDSONALPHA INSTITUTE FOR BIOTECHNOLOGY

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