Ultrastructural Variations in Platelets and Platelet Mitochondria: A Novel Feature in Amyotrophic Lateral Sclerosis

Platelets are characterized as a systemic tool to elucidate mitochondria-allied perturbance in neurological diseases. The authors studied ultrastructural changes in platelets and platelet mitochondria using a case-control approach in amyotrophic lateral sclerosis (ALS). Subjects were sporadic ALS cases (n = 22) and age- and sex-matched controls (n = 16). Phlebotomy was performed, platelet concentrates (PCs) were prepared, and mitochondria were extracted. PCs and mitochondria were processed for ultrastructure study using transmission electron microscopy. Image analysis was done using Image-J. Transmission electron microscopy demonstrated both qualitative and quantitative variations in ALS platelets and platelet mitochondria. Heterogeneous distribution of granules, formation of vacuoles, blebs, pseudopodia, loose demarcation of cell membrane with a significant increase in area (20.3%), perimeter (17.82%), integrated density (21.44%), electron-lucent granules (41.79%), and vacuoles (36.58%) were observed in ALS platelets. Conversely, control platelets exhibited an increase of circularity (11.7%) and electron-dense granules (36.89%). In parallel, nonuniformity of matrix, faint cristae, greater lysosomal bodies, and lesser intramitochondrial granules were seen in ALS platelet mitochondria. Significantly greater area (26.88%), perimeter (15%), circularity (3.76%), and integrated density (25.18%) were observed in control platelet mitochondria. Ultastructural divergence in platelets of ALS patients underlines a potential dependence of platelets on modest mitochondrial functioning. These observations also support the view that systemic involvement might be a novel feature in ALS pathophysiology.