Yingratana (Belle) McLennan

My study investigates glial cell pathology in the frontal cortex of individuals with Fragile X–associated Tremor/Ataxia Syndrome (FXTAS), with a focus on white matter degeneration. Using histology and principal component analysis, I identified coordinated patterns of astrocyte degeneration, mature oligodendrocyte loss, and demyelination. These findings highlight glial dysfunction as a central driver of white matter disease in FXTAS.

Fragile X–associated Tremor/Ataxia Syndrome (FXTAS) is a late-onset neurodegenerative disorder characterized by motor and cognitive decline, with prominent white matter abnormalities. This study examines glial pathology in the prefrontal cortex of FXTAS patients compared to age-matched controls, focusing on astrocytes and oligodendrocyte lineage cells. Using quantitative immunohistochemistry and principal component analysis, I identified a coordinated pattern of white matter–associated degeneration defined by increased degenerative and reactive astrocytes, loss of mature oligodendrocytes, and demyelination. These changes strongly cluster in FXTAS cases and distinguish them from controls, suggesting a shared pathological axis driven by glial dysfunction. Additionally, the accumulation of intranuclear inclusions within astrocytes and oligodendrocytes further supports widespread cellular stress in white matter regions. Together, these findings demonstrate that glial degeneration is not secondary but a defining feature of FXTAS pathology. This work highlights astrocytes and oligodendrocytes as critical contributors to disease progression and potential targets for therapeutic intervention.