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Alzheimer's disease is the most common type of age-related dementia. Amyloid plaques and tau tangles are the two pathological features of the disease. A new study in mice shows that a new DNA-based vaccine administered to the skin triggers an immune response that reduces the accumulation of tau and beta-amyloid proteins.
Toxic amyloid plaques (in red) and tau tangles (in brown) form on the brain of a mouse with the impact of Alzheimer's disease. Image credit: University of Texas Southwestern.
The new vaccine is on a short list of promising antibody treatments to protect against the two types of proteins that destroy brain cells when they spread to deadly plaques and tangles in the brains of patients with Alzheimer's disease.
"Our study is the result of a decade of research that has repeatedly shown that this vaccine can safely and effectively target animal models to what we believe to be the cause of Alzheimer's disease. I think we're about to test this therapy on people, "said Dr. Roger Rosenberg, lead author of the study, founding director of the Alzheimer's Disease Treatment Center at the University of Texas Southwestern. .
Although previous research has established that antibodies significantly reduce amyloid buildup in the brain, Dr. Rosenberg and his colleagues needed to find a safe way to introduce them into the body.
A vaccine appeared promising in the early 2000s, but when tested in humans, it caused brain swelling in some patients.
The idea of the team was to start with the amyloid coding DNA and inject it into the skin rather than into the muscle to produce a different type of immune response.
The injected skin cells form a chain of three beta-amyloid molecules (Aβ42), and the body reacts by producing antibodies that inhibit amyloid formation and, indirectly, tau.
The study, consisting of four cohorts of 15 to 24 mice each, shows that the vaccine resulted in a 40% reduction in beta-amyloid and up to 50% in tau protein, with no unwanted immune response .
"If amyloid and tau are the cause of Alzheimer's disease, getting these reductions in humans could be of major therapeutic value," said Dr. Rosenberg.
"If the onset of the disease could be delayed for five years, it would be huge for patients and their families. The number of cases of dementia could drop by half, "said Dr. Doris Lambracht-Washington, senior author of the study, also from the University of Texas, in the south-west of the country.
"Allowing the body to produce its own antibodies through active immunization would be the preferred strategy, if it can be done safely. Among the benefits, the vaccine would be more accessible and less expensive, "added Dr. Rosenberg.
"It also produces a wider variety of types of antibodies than preformed antibodies containing a single specific antibody."
The results are published in the journal Alzheimer's Research and Therapy.
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Roger N. Rosenberg et al. 2018. Active immunization to full-length DNA by 3xTg-AD mice not only reduces amyloid deposition, but also the pathology of tau protein. Alzheimer's Research and Therapy 10: 115; doi: 10.1186 / s13195-018-0441-4
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