Tau and Beta-Amyloid Disrupt Memory and Emotions Differently in Alzheimer’s

Researchers from the Institut de Neurociències of the Universitat Autònoma de Barcelona (INc-UAB) have found that tau protein and beta-amyloid – two pathological hallmarks of Alzheimer’s disease – affect the brain in different yet complementary ways. The study, conducted in collaboration with the Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED) and the Universidad Pablo de Olavide (UPO), provides new insight into how these proteins disrupt brain circuits related to memory and emotions.

Published in Molecular Psychiatry, the research demonstrates that tau accumulation in the hippocampus contributes to memory deficits, while beta-amyloid buildup in the amygdala is associated with emotional disturbances such as anxiety and fear. Additionally, when both proteins are present, they amplify brain inflammation and dysfunction, exacerbating the disease’s effects.

Rethinking Alzheimer’s disease mechanisms

Alzheimer’s research has historically been dominated by two main theories: one proposing that tau accumulation inside neurons drives disease progression, and another suggesting that beta-amyloid buildup is the primary cause. These perspectives have shaped treatment strategies, which generally focus on targeting one of these proteins to slow disease progression.

However, the study’s findings suggest that these pathologies work in tandem, supporting the idea that a dual-targeted therapeutic approach may be necessary to address Alzheimer’s disease more effectively.

A new mouse model for studying Alzheimer’s disease

The research team developed a transgenic mouse model that exhibits both tau and beta-amyloid pathologies. Traditionally, animal models used in Alzheimer’s research focus on only one of these proteins, limiting the ability to study their combined effects. By designing a model that replicates both tau and beta-amyloid accumulation, the researchers were able to analyze how these proteins interact and contribute to neurodegeneration.

Implications for future treatments

The study’s results suggest that a more comprehensive treatment strategy, targeting multiple disease mechanisms such as phosphorylated tau and beta-amyloid, could be more effective in slowing Alzheimer’s progression. While additional research is needed to determine whether these findings translate to human patients, the study represents an important step toward developing new therapeutic approaches for the disease.

Reference: Capilla-López MD, Deprada A, Andrade-Talavera Y, et al. Synaptic vulnerability to amyloid-β and tau pathologies differentially disrupts emotional and memory neural circuits. Mol Psychiatry. 2025. doi: 10.1038/s41380-025-02901-9

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