A team of researchers has uncovered that the two main pathological features of Alzheimer’s disease, tau protein and beta-amyloid, impact brain circuits in different yet complementary ways, especially in areas associated with memory and emotions. The investigation, utilizing a novel animal model of Alzheimer’s, hints at a significant advancement in potential treatment strategies. Present treatments primarily target only one of the harmful proteins that contribute to the disease; however, this finding could lead to more holistic treatment methods.
A team of researchers from the Institut de Neurociències of the Universitat Autònoma de Barcelona (INc-UAB) has identified that the two principal pathological markers of Alzheimer’s—tau protein and beta-amyloid—affect brain circuits differently but in a way that enhances each other’s impact, particularly regarding memory and emotions. This research was done in partnership with the Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED) and the Universidad Pablo de Olavide (UPO).
In a study published in Molecular Psychiatry (part of the Nature group), the researchers found that excess tau in the hippocampus is linked to memory issues, whereas the accumulation of beta-amyloid in the amygdala leads to emotional problems such as anxiety and fear—two early indicators of Alzheimer’s. Additionally, when both pathologies are present, they significantly increase brain inflammation and dysfunction, amplifying their effects.
For years, Alzheimer’s research has been framed by two main hypotheses: one suggesting that the disease starts from tau buildup inside neurons, and the other attributing it mainly to the accumulation of beta-amyloid. These theories have heavily influenced the current treatment strategies, which typically aim to inhibit the buildup of either tau or beta-amyloid in an attempt to slow the disease’s progression. However, the team of researchers, led by Carles Saura and Arnaldo Parra-Damas from the UAB Department of Biochemistry and Molecular Biology and the INc-UAB, suggests that targeting both proteins simultaneously could be essential for effectively addressing the disease.
This breakthrough was made possible by creating a new transgenic mouse model that mimics both tau and beta-amyloid pathologies. “Although both proteins are found in the brains of Alzheimer’s patients, most animal models used in research usually focus on just one of them,” states Maria Dolores Capilla, the principal author of the study. “In our analysis, we developed a transgenic mouse model that displays both tau and beta-amyloid accumulation, which allowed us to investigate their separate and combined effects,” adds the INc-UAB researcher.
These results have the potential to transform current treatment methodologies, which frequently focus solely on one of these detrimental proteins. “Current therapies have not demonstrated clear clinical improvements. Our findings indicate that a treatment approach tackling multiple disease mechanisms—like phosphorylated tau and beta-amyloid—might yield better results,” concludes Carles Saura.
Although further research is required to determine how these findings relate to human patients, this study marks a significant advance toward exploring new avenues for Alzheimer’s treatment, according to the research team.
