Abstract:

INTRODUCTION: Chromosome 9 open reading frame 72 (C9orf72) is an evolutionarily conserved protein with unknown function, expressed at high levels in the brain. An expanded hexanucleotide GGGGCC repeat located in the first intron of the C9orf72 gene represents the most common genetic cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Previous studies by immunohistochemistry with two different anti-C9orf72 antibodies named sc-138763 and HPA023873 showed that C9orf72 is expressed chiefly in the cytoplasm of neurons, and is concentrated in the synaptic terminals in the brains of FTD/ALS with or without C9orf72 repeat expansion as well as those of controls. At present, a pathological role of C9orf72 in the process of neurodegeneration remains unknown.
METHODS: Using immunohistochemistry we studied C9orf72 expression in the frontal cortex and the hippocampus of six Alzheimer's disease (AD) and 13 control cases, including ALS, Parkinson's disease, multiple system atrophy, and non-neurological cases.
RESULTS: The HPA023873 antibody showed a cross-reactivity to glial fibrillary acidic protein, and therefore stained intensely reactive astrocytes in AD and non-AD brains. Both sc-138763 and HPA023873 antibodies labeled the neuronal cytoplasm and the neuropil with variable intensities, and intensely stained a cluster of p62-negative, UBQLN1-positive swollen neurites, which were distributed in the CA1 region and the molecular layer in the hippocampus of both AD and non-AD brains. Most notably, both of these antibodies reacted strongly with dystrophic neurites accumulated on senile plaques in AD brains.
CONCLUSION: These results suggest a general role of C9orf72 in the process of neurodegeneration in a range of human neurodegenerative diseases.

日本語要旨:

C9orf72遺伝子の第一イントロンのhexanucleotide GGGGCC repeatはFTDとALSの遺伝的な原因の一つであることが報告されている。我々はアルツハイマー病と対照脳を抗C9orf72抗体(sc-138763とHPA023873)で免疫組織化学的に検索し、アルツハイマー病の変性軸索(特に老人斑周囲の変性軸索)が陽性を示すことを見出した。