A new investigation by the journal Science casts doubt on a series of high-profile findings claiming that rare genetic variants protect against Alzheimer's disease — discoveries that helped galvanize the field around the idea that a single gene's hidden defense could inspire a cure.
The investigation, by reporters Charles Piller and Jennie Erin Smith, focuses on a decades-long program studying members of a large extended family in Colombia who carry a genetic mutation that causes dementia before age 50. In 2019, researchers made headlines by revealing that a mutation called APOE3 Christchurch appeared to protect one woman carrying the disease-causing mutation from developing memory loss until her early 70s. In 2023, the same group announced a second apparently protective mutation, Reelin-COLBOS, discovered in the same Colombian kindred; a third purported example has not yet been published.
The discoveries won professional accolades and tens of millions of dollars in research funding for the married couple at the center of the work: ophthalmology researcher Joseph Arboleda-Velasquez of Harvard Medical School and Mass Eye and Ear, and neuropsychologist Yakeel Quiroz of Boston University and Massachusetts General Hospital. They also inspired a wave of efforts to develop therapies that mimic the natural protection.
But after reviewing scholarly papers, patents, grant data and communications between key researchers — and interviewing insiders, collaborators and independent experts — Piller and Smith report that the group appears to have embraced a questionable approach to identifying protective mutations, improperly changed patient data in ways that bolstered provocative findings, and published seemingly altered or copied images in multiple papers.
The implications extend beyond the specific mutations. The findings had shaped research priorities, influenced the standing of competing hypotheses about Alzheimer's mechanisms, and directed tens of millions in funding. Independent experts cited in the investigation say the doubts raised about the central human genetic evidence weaken the case for prioritizing this line of research. Science's news team reported the investigation as an exclusive, and the researchers at the center of the work have been approached for comment as the journal continues to examine the claims.
