TDP43 pathology in the brain, spinal cord, and dorsal root ganglia of a patient with FOSMN

Abstract

Objective: To describe the histopathologic features of a case of facial-onset sensory and motor neuronopathy (FOSMN).

Methods: We describe a postmortem examination performed on a 54-year-old man with FOSMN associated with personality change.

Results: Postmortem examination revealed TAR DNA-binding protein (TDP) 43 proteinopathy with widespread distribution. TDP43 pathology was seen in the neurons and glial cells and was most pronounced in the subthalamic nucleus followed by the spinal cord, including dorsal root ganglia, brainstem, and other deep cerebral nuclei. In the medial temporal lobe, neocortex and subcortical hemispheric white matter TDP43 pathologic inclusions were very rare. In contrast to TDP43 pathologies associated with typical amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD)-TDP, in this case, there were more frequent TDP43-positive oligodendroglial, coiled body-like cytoplasmic inclusions than neuronal inclusions. Neuronal cytoplasmic TDP43 inclusions with globular and skein-like morphology were seen in both anterior horn cells and dorsal root ganglia. No β-amyloid, α-synuclein, or significant hyperphosphorylated tau pathology was seen.

Conclusion: This case provides further evidence that FOSMN is a neurodegenerative disease characterized by TDP43 pathology. Despite minimal cortical TDP43 pathology, the clinical features of the behavioral variant of FTD in this patient suggest that FOSMN may fall within or overlap with the FTD-ALS spectrum.

Figure. TDP43 proteinopathy in FOSMN

(A) Pathologic thread-like deposits in a neuron within dorsal root ganglion. (B) Globular cytoplasmic inclusion in the lumbar anterior horn motor neuron. (C) Large globular and skein-like (inset) cytoplasmic inclusions in pigmented neurons of the substantia nigra. (D–F) Various morphologies of neuronal cytoplasmic inclusions. (G– I) glial cytoplasmic inclusions, all of which show similar, coiled body–like morphology. (J–L) Appearances of dystrophic neurites, all of which are short and curved with no evidence of long neurites. All sections are immunostained with nonphosphorylated TAR DNA-binding protein 43 (TDP43) antibody, which detects normal nuclear TDP43 labeling and shows absent nuclear labeling in cells where there is TDP43 mislocalization from the nucleus to cytoplasm or cell processes. Scale bar: 10 μm in panels A–L. FOSMN = facial-onset sensory and motor neuronopathy.