The Comparative Pathogenesis of Alzheimer's Disease and Related Disorders Laboratory led by Casey N. Cook, Ph.D., is focused on identifying common pathological mechanisms across a spectrum of disorders. In particular, the overall goal of the laboratory is to provide new insight into pathogenic mechanisms of Alzheimer's disease (AD) and related disorders and elucidate novel therapeutic strategies to treat them. To achieve these goals, the lab uses cell and animal models, as well as human biofluids and postmortem tissue samples.
- Evaluating mechanisms of neurodegeneration in tauopathy. Accumulation of the tau protein is a major pathological hallmark of AD and other neurodegenerative diseases classified as tauopathies, but the mechanisms of tau aggregation and resultant toxicity remain unclear. To investigate pathogenic mechanisms common across tauopathies, Dr. Cook's lab develops and applies new mouse models of familial and sporadic disease, followed by validation of novel discoveries in human tissue samples.
- Pathogenic mechanisms in TDP-43 proteinopathy. Aggregation of the TDP-43 protein is observed in the majority of AD cases and is also a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Because a repeat expansion in the C9orf72 gene is the most common genetic cause of FTD and ALS, Dr. Cook and her colleagues at Mayo Clinic use the C9orf72 repeat expansion to provide insight into the mechanisms contributing to TDP-43 proteinopathy in patients.
- Investigating white matter abnormalities in neurodegeneration. Defects in myelination are a common pathological feature of AD and related disorders, but the involvement of myelin-producing cells in the brain (oligodendrocytes) and their precursors in disease pathogenesis remains relatively unexplored. In collaboration with colleagues, Dr. Cook's laboratory aims to provide new insight into the role of oligodendrocyte lineage cells in neurodegeneration.
Significance to patient care
The lack of effective treatments for most neurodegenerative diseases makes their diagnosis particularly devastating to patients. To address this need and facilitate the discovery of novel treatment strategies and biomarkers, Dr. Cook's research is focused on understanding the underlying causes of neurodegeneration. In particular, by mapping specific molecular routes that lead to AD and related disorders, effective strategies to detour disease progression can be identified, with key landmarks providing ideal targets for biomarkers of disease status.