Molecular Neurobiology Unit, Fondazione Santa Lucia, Rome, ITALY
Patient-Derived Fibroblasts Model Aspects of Progressive Supranuclear Palsy
Host: E. Buratti
The seminal work published in 1963 by Drs. Richardson, Olszewski and Steele detailing a series
of patients with postural instability, ocular motor abnormalities, facial and cervical dystonia
and dementia, was the first to describe an “heterogeneous system degeneration” now
called Progressive Supranuclear Palsy (PSP). The initial neuropathologic findings described
argyrophyllic globose and flame-shaped inclusions in both the gray and white matter
throughout brainstem, subcortical and neocortical regions with neuronal loss and white
matter degeneration. Immunohistochemistry studies revealed that these inclusions were
accumulations in neurons and glial cells of the microtubule associated protein TAU in a variety
of morphologies. Alternative splicing generates six isoforms of the TAU protein. Treatment is
still largely supportive.
In the present study, primary cultures of human fibroblasts were established from 7 patients and
4 controls. PSP fibroblasts present hyperphosphorylated TAU aggregates in the cytosol (peri-
nuclear area) and in the nucleus and a decreased proliferation rate compared to the controls.
Furthermore, PSP patient–derived fibroblasts show significantly increased mitochondrial
oxygen consumption parameters.
Altogether, our results show molecular defects in a peripheral tissue of patients and suggest
that fibroblasts can, therefore, be useful in modelling pathways linked to the TAU pathology
and PSP neurodegeneration.
International Seminar Programme
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