Researchers have discovered a unique case in a Colombian family where a woman with a genetic predisposition to Alzheimer’s disease remained cognitively healthy due to a rare APOE gene mutation, the Christchurch mutation. This mutation disrupts the typical progression of Alzheimer’s disease and suggests new prevention strategies. Dementia may be prevented by breaking the link between early and late stages of the disease.
The disease has plagued one large Colombian family for generations, killing half of them in their prime years. But one member of the family avoided what seemed like fate. She remained cognitively healthy well into her 70s, even though her relatives inherited her genetic defect that caused her to develop dementia in her 40s.
Researchers at Washington University School of Medicine in St. Louis now think they know why. Previous research had reported that the woman was in possession of two copies of the rare variant, unlike her relatives. Apoe A gene known as the Christchurch mutation.
In this study, researchers used genetically modified mice to show that the Christchurch mutation was associated with early stages of Alzheimer’s disease, when a protein called amyloid beta accumulates in the brain, and another protein called tau, which causes cognitive impairment. begins to decline. So the women remained mentally alert for decades, even though their brains were filled with large amounts of amyloid.
“All protective factors are very interesting because they give us new clues about how the disease works,” said lead authors Barbara Barton, Ph.D., and Reuben M. said David M. Holzman, M.D., Morris III Professor Emeritus of Neurology.
Understanding the progression of Alzheimer’s disease, the researches found thatthe main difference was the level of activity of microglia, the brain’s waste-processing cells. Microglia tend to cluster around amyloid plaques. In mice with Apoe The Christchurch mutation activated microglia surrounding amyloid plaques, making them highly efficient at consuming and processing tau aggregates.
Reference: “APOE3ch alters microglial responses and suppresses Aβ-induced tau dissemination and spread” Yun Chen, Sihui Song, Samira Parhizkar, Jennifer Lord, Yiyang Zhu, Michael R. Strickland, Chanung Wang, Jiyu Park, G By Travis Tabor, Hong Jiang, Kevin Lee, Albert A. Davis, Carla M. Huede, Marco Colonna, Jason D. Ulrich, David M. Holtzman, December 11, 2023. cell.DOI: 10.1016/j.cell.2023.11.029
Source: scitechdaily.com
