Defining Immunometabolic Contributions to Cognitive Impairment in Alzheimer's Disease

In this study, I aim to determine how the protein p38-alpha MAPK regulates the neurobiological network between neurons and supportive cells in the central nervous system to govern cognitive decline in Alzheimer’s disease.

Certain molecules within different brain cells can govern metabolic processes that modulate the progression of Alzheimer’s disease and dementia. In this study, I have identified a molecule, referred to as p38MAPK, in a supportive brain cell type, known as astrocytes, that may regulate the neurobiological network involved in cognitive decline in Alzheimer’s disease. Therefore, I am proposing to use cutting-edge neuroscience techniques to eliminate production of p38MAPK in such astrocytes brain cells in attempt to slow disease and dementia progression in a mouse model of Alzheimer’s disease.

Identifying temporal dynamics of AD-like pathology is a crucial feature in determining antagonistic immunometabolic features accompanying amyloid beta deposition, research best practices, and translational therapeutic strategies. This study undertakes this pursuit by placing p38a MAPK at the nexus of understanding these dynamics with the added advantage of nuanced operant behavioral techniques that can be directly translated to human behavior. Such behavioral techniques are seldom incorporated in pre-clinical AD research despite their utility in providing fine-grain resolution of behavioral divergences underlying aberrant cognition in diseased states, such as AD.

P38a MAPK is a well-documented protein involved in pathological progression and systems dysfunction AD. However, this study is unique in that we are aiming to target p38 MAPK in an early window of AD pathological detection that would provide substantive proof-of-concept for developing therapeutic strategies to enhance the function non-neuronal support cells across AD progression. In this pursuit, this study would imply that intervention proximal to early detection of AD pathology could diminish immunometabolic dysfunction, neuronal damage, and cognitive decline despite amyloid beta burden.