Alzheimer’s disease (AD) stands as an age-dependent chronic neurodegenerative condition marked by the accumulation of aberrant proteins in the brain (amyloid and tau), resulting in memory loss and cognitive decline. Notably, before the manifestation of detectable brain plaques and noticeable behavioral changes, there is an onset of dysfunctional neuronal activity. This aberrant neuronal electrical activity seems to contribute to an accelerated degeneration of brain tissue, ultimately leading to irreversible cognitive deterioration. A potential detrimental cycle unfolds in early AD stages: The disease-induced production of toxic materials (amyloid and tau) triggers heightened neuronal activity in specific brain regions. Subsequently, this aberrant neuronal activity, in turn, amplifies the production of the same toxic materials (amyloid and tau). This project aims to unravel the intricacies of the neural circuit components that are sensitive to increased levels of amyloid and tau, particularly in animal models of Alzheimer’s disease. Our focus is on probing the early stages of AD, a phase preceding significant protein plaque accumulation that inflicts irreparable damage to brain structures. By identifying the vulnerabilities within the neural circuitry, we aim to pave the way for the development of therapeutic approaches capable of safeguarding these circuits from the ongoing pathology of AD. The ultimate goal is to intervene at a critical juncture, mitigating the impact of neurodegeneration and potentially offering novel avenues for effective treatment and prevention strategies for Alzheimer’s disease.
Alzheimer’s disease (AD) is an age-dependent chronic neurodegenerative disease, characterized by accumulation of aberrant proteins in the brain (amyloid beta and tau), loss of memory and cognitive capacity. At early stages of disease, prior to the detection of brain plaques and significant behavioral changes, a dysfunctional neuronal activity begins to emerge, and it appears that this neuronal electrical activity promotes faster degeneration of the brain tissue, leading to irreversible cognitive deterioration. A vicious downward cycle thus may exist: initially, the AD-mediated production of toxic materials (amyloid beta and tau) triggers stronger neuronal activity in some parts of the brain circuit, and then this aberrant neuronal activity accelerates the production of the same toxic materials (amyloid beta and tau). This project seeks to determine the components of the neural circuit that are sensitive to increased levels of amyloid beta and tau in animal models of AD. We are especially keen to investigate early stages of AD, before a significant accumulation of protein plaques inflicts irreparable damage to the brain structures. Once we identify the vulnerabilities in the brain circuit, we might then be able to develop therapeutic approaches to protect these neural circuits from the ongoing AD pathology.