People with Down syndrome are at high risk of developing a dementia very similar to that caused by Alzheimer’s disease. This has been seen in a study published in the journal PNAS that has found that, in these people, and as had been observed in “classic” Alzheimer’s, the characteristic proteins of the disease have prion characteristics.
Researchers at the University of California-San Francisco (USA) say that a better understanding of the Aβ and tau prions in Down syndrome may improve the design of clinical trials of potential treatments for Alzheimer’s disease.
It is known that from the age of 40, people with Down syndrome develop a progressive dementia similar to Alzheimer’s.
Because previous analyzes of brain samples had already shown that both Down syndrome and Alzheimer’s are characterized by extracellular amyloid plaques made of Aβ and intracellular neurofibrillary tangles made of tau, the team Carlo Condello and Stanley Prusiner investigated whether there were other molecular characteristics similar to Alzheimer’s dementia in Down syndrome, and the answer was positive.
Specifically, the researchers saw that they share similarities in the Aβ and tau prion proteins.
Prions, they explain, induce misfolding of additional copies of the native protein in a self-perpetuating process that extends within and between neuronal cells.
The brains of people with Down syndrome contained Aβ and tau prions that were indistinguishable from those found in Alzheimer’s.
The research found that almost all brain samples from 28 deceased individuals who had Down syndrome and whose ages ranged from 19 to 65 years had measurable levels of Aβ and tau prions.
Using cell bioassays, the authors found that the brains of people with Down syndrome contained Aβ and tau prions that were indistinguishable from those found in Alzheimer’s.
However, Aβ and tau prion levels increased with age in Down syndrome but decreased with age at death in Alzheimer’s.
According to the authors, a better understanding of Aβ and tau prions in Down syndrome could improve the design of clinical trials of potential treatments for Alzheimer’s, reducing both the number of patients and the length of the trial needed to gain meaningful insights.
As Jesús Flórez, Professor of Pharmacology at the University of Cantabria, explains to the Science Media Center, the study “confirms previous work in which it is seen that A-beta proteins and tau proteins can acquire the characteristics of prions and, in this way, , contribute to the expansion of these proteins in the brain, favoring the formation of amyloid plaques and neurofibrillary tangleswhich are characteristic lesions of Alzheimer’s disease.
For the also president of the Ibero-American Down Foundation21, the work “reveals the precocity of the appearance of such proteins with prion properties in Down syndrome”. And he concludes that it is “one more piece of information to consider in the pathogenesis of Alzheimer’s disease in Down syndrome.”