Mutations in the fused in
sarcoma (FUS) gene are linked to a form of familial
amyotrophic lateral sclerosis (ALS), ALS6. The
FUS protein is a major component of the
ubiquitin-positive neuronal cytoplasmic inclusions in both ALS6 and some rare forms of
frontotemporal lobar degeneration (
FTLD). The latter are now collectively referred to as
FTLD-FUS. In the present study, we investigated the localization of FUS in human and mouse brains. FUS was detected by western blot as an approximately 72 kDa
protein in both human and mouse brains. Immunohistochemistry using lightly fixed tissue sections of human and mouse brains revealed FUS-positive granular staining in the neuropil, in addition to nuclear staining. Such granules are abundant in the gray matter of the brainstem and spinal cord. They are not frequent in the telencephalon. At the light microscopic level, FUS-positive granules are often co-localized with
synaptophysin and present in association with
microtubule-associated protein 2-positive dendrites. In the synaptosomal fraction of mouse brain, FUS is detected mainly in the post-synaptic density fraction. Thus, while FUS is primarily a
nuclear protein, it may also play a role in dendrites. In the brains of patients with
FTLD with TDP-43 deposition (
FTLD-TDP), the number of FUS-positive granules in the cortex is increased compared with control cases. The increase in
Alzheimer's disease (AD) is less remarkable but still significant. The dendritic localization of FUS and its increase in
FTLD-TDP and AD may have some implication for the pathophysiology of
neurodegenerative diseases.