alpha-Synuclein Aggregates with beta-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily alpha-synuclein (alpha-syn), beta-amyloid(1-42) (A beta), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of alpha-syn interactions with A beta or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral alpha-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of alpha-syn, A beta, tau, and of their heterocomplexes was determined in red blood cells (RBCs) of healthy subjects (sedentary and athletes). Such parameters were related to the extent of the antioxidant capability (AOC), a key marker of oxidative stress in aging-related pathologies, and to physical exercise, which is known to play an important preventive role in NDs and to modulate oxidative stress. Tau content and plasma AOC toward hydroxyl radicals were both reduced in older or sedentary subjects; in contrast, alpha-syn and A beta accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, alpha-syn heterocomplexes with A beta or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, alpha-syn/A beta aggregates were significantly reduced in athletes and inversely correlated with physical activity level, independent of age. The positive correlation between antioxidant capability/physical activity and reduced protein accumulation was confirmed by these data and suggested that peripheral alpha-syn heterocomplexes may represent new indicators of ND-related protein misfolding.