Share this to:

Support & Insight for the Autumn of Life

Neuroarchaeologists Uncover Original Alzheimer’s Gene Mutation

DNA made of genes

The age and origin of an Alzheimer’s gene mutation has been traced to a single founder dating from the 16th century. E280A is responsible for early-onset Alzheimer’s in a Colombian family with an unusually high incidence of the disease. Find out how researchers solved this puzzle of the past and why it may be useful in the future.

Kenneth S. Kosik, Harriman Professor in Neuroscience at UC Santa Barbara and co-director of the campus’s Neuroscience Research Institute (NRI), conducted the study. The findings appear in the journal Alzheimer’s & Dementia.

“Some mutations just increase your risk, but this mutation is not a risk,” Kosik said. “This mutation is highly penetrant, which means that if you carry the mutation, you will get early-onset Alzheimer’s disease.”

Kosik’s team sequenced the genomes of more than 100 family members and applied identity-by-descent analysis to identify regions of common ancestry. DNA is inherited from both the parents and recombined in chunks. From these pieces, scientists can identify which parent — and sometimes which grandparent or great-grandparent — is the source of the DNA. As time goes by, sections of DNA recombine into smaller and smaller segments, each representing a history of its ancestry.

Sequencing the genomes came about because the researchers knew that while most family members with the mutation develop early-onset Alzheimer’s at age 45, there were a small number of outliers. “A few people got it a decade later, a few got it a decade earlier and we wondered if there was a gene that was protecting those who got the disease later,” Kosik explained. “That protective gene — even though this mutation exists only in this Colombian family — might be useful for all of us. That research is still ongoing.”

Out of the genome sequencing came the idea of determining where the gene mutation originated. In addition to DNA analysis, the researchers conducted interviews with the older healthy individuals of each affected family and spoke to genealogists and historians in Colombia’s Antioquian region. Kosik’s co-author Francisco Lopera examined local historical and genealogical books, last wills and ecclesiastical records dating as far back as 1540.

When the scientists examined the DNA patterns around the gene mutation site, they found markers from the Iberian peninsula. They estimated the age and geographic origin of E280A to be consistent with a single founder dating from the time of the Spanish Conquistadors who began colonizing Colombia during the early 16th century.

“This doesn’t have big medical implications, but it shows that genetics is a very powerful tool and can be used to reconstruct history,” Kosik said. “What we’ve done here might be called ‘neuroarchaeology.’ ”


University of California – Santa Barbara, by Julie Cohen.

Journal Reference:

  1. Matthew A. Lalli, Hannah C. Cox, Mary L. Arcila, Liliana Cadavid, Sonia Moreno, Gloria Garcia, Lucia Madrigal, Eric M. Reiman, Mauricio Arcos-Burgos, Gabriel Bedoya, Mary E. Brunkow, Gustavo Glusman, Jared C. Roach, Leroy Hood, Kenneth S. Kosik, Francisco Lopera. Origin of the PSEN1 E280A mutation causing early-onset Alzheimer’s disease. Alzheimer’s & Dementia, 2013; DOI:10.1016/j.jalz.2013.09.005
Notify of

Inline Feedbacks
View all comments
December 11, 2013 10:03 pm

so are you suggesting that the Colonization had an effect on the mutation, i.e. a Conquistador impregnating a Colombian native?

December 12, 2013 1:33 am

My sister is 56 y/o & she was diagnoised when she was 52, now losing her neurological function

B. Berger

B. Berger

Visit Our Pages On:


This site was inspired by my Mom’s autoimmune dementia.

It is a place where we separate out the wheat from the chaffe, the important articles & videos from each week’s river of news. With a new post on Alzheimer’s or dementia appearing on the internet every 7 minutes, the site’s focus on the best information has been a help to many over the past 15 years. Thanks to our many subscribers for your supportive feedback.

The site is dedicated to all those preserving the dignity of the community of people living with dementia.

Peter Berger, Editor


person wearing hearing aid
Can Hearing Aids Diminish Dementia?
Hearing loss and dementia may be linked, but there is a silver lining here.
Black tweezers on white background.
CLR01 Beats Curcumin in Blocking Alzheimer's
CLR01, a "molecular tweezer", keeps brain proteins from the clumping, or aggregating, that causes Alzheimer's, Parkin...
Researching the Brain
Gene Allele DR4 Fends off Alzheimer's AND Parkinson's
"The night after we found that out, I couldn’t sleep," said Senior Researcher Dr. Emmanuel Mignot. 1 in 5 people have...
Would love your thoughts, please comment.x
News, Treatments, Care Tips

Subscribe To The Weekly Newsletter

videos & articles on Research & Prevention
News to Get at the Truth

Subscribe To Our Weekly Newsletter