Neuronal inclusions of alpha-synuclein contribute to the pathogenesis of Krabbe disease

SMITH BD; SANTOS MB; MARSHAL MS; CANTUTI-CASTELVETRI L; LOPEZ-ROSAS A; LI G; VAN BREEMEN R; CLAYCOMB KI; GALLEA JI; CELEJ MS; CROCKER S; GIVOGRI MI; BONGARZONE ER

The Journal of Pathology

Wiley

Año: 2014

1096-9896

emyelination is a major contributor to the general decay of neural functions in children with Krabbe disease. However, recent reports have indicated a significant involvement of neurons and axons in the neuropathology of the disease. In this study, we have investigated the nature of cellular inclusions in the Krabbe brain. Brain samples from the Twitcher mouse model for Krabbe disease and from patients affected with the infantile and late onset forms of the disease were examined for the presence of neuronal inclusions. Our experiments demonstrated the presence of cytoplasmic aggregates of thioflavin-S reactive material in both human and murine mutant brains. Most of these inclusions were associated with neurons. A few inclusions were detected to be associated with microglia and none were associated with astrocytes or oligodendrocytes. Thioflavin-S reactive inclusions increased in abundance paralleling the development of neurological symptoms and distributed throughout the Twitcher bra