The histopathological evaluation of motor neuron tissue in ALS reveals hallmark cellular inclusions and structural alterations. Among these pathological hallmarks, Bunina bodies stand out as a definitive pathological signature of ALS.
Bunina Bodies: Morphology and Pathognomonic Significance
First identified by Tat'yana Bunina, a neuropathologist from the USSR who initially hypothesized a viral etiology, Bunina bodies are now recognized as pathognomonic histopathological features of ALS.
Bunina Body Characteristics:
• Appearance: Bright pink, oval eosinophilic inclusions on H&E staining
• Internal Structure: Central clear zones, frequently appearing in small clusters
• Distribution: Located within cytoplasm and dendrites; ABSENT in the axoplasm
• Anatomic Site: Motor neurons of the spinal cord and brainstem motor nuclei
Organelle Involvement and Biogenesis
Pathological studies link Bunina body formation to Golgi complex dysfunction and nucleic acid dysmetabolism at the rough endoplasmic reticulum (rER). Structural fragmentation of the Golgi apparatus often precedes inclusion formation, highlighting endomembrane system disruption.
Proteinopathy and TDP-43 Inclusions
In addition to Bunina bodies, modern ALS neuropathology emphasizes major proteinaceous inclusions:
TDP-43 Aggregates: Ubiquitinated hyperphosphorylated cytoplasmic inclusions present in >95% of sporadic ALS cases.
FUS Inclusions: Characteristically present in specific FUS-mutation driven forms.
SOD1 Inclusions: Distinct protein aggregates observed in SOD1-mediated FALS.
Key Takeaways
Bunina bodies are pathognomonic eosinophilic inclusions in ALS motor neurons.
They are present in the soma and dendrites, but absent from the axoplasm.
Biogenesis is closely tied to Golgi complex breakdown and rER metabolic dysfunction.