Widespread and abundant α‐synuclein pathology in a neurologically unimpaired subject

The intracytoplasmic aggregation of α‐synuclein (αS) protein is a common denominator for a group of neurodegenerative disorders currently known as synucleinopathies. It is generally assumed that the incorporation of αS protein into compact inclusions compromises the function and viability of its host cell via mechanical disruption. Herein, we report a widespread and abundant αS pathology in an elderly subject, whose medical history gave no indication of any neurodegenerative disease. We compared neuronal and glial components in this neurologically unimpaired subject with a patient with a clinical syndrome of dementia with Lewy bodies (DLB) by using a range of antigenic determinants and an in situ end‐labeling technique. We detected no differences in vascular pathologies, in gliosis, or in apoptosis that would have explained the incompatible clinical end‐points. With respect to the Alzheimer's disease‐related changes, the only differences noted were the β‐amyloid aggregates in the putamen found in the DLB patient alone. Our findings suggest that there must be some currently unidentified factors rather than αS‐positive inclusions that are responsible for the neuronal dysfunction. The αS‐positive inclusions may well represent detoxified reserves that cells can tolerate for years, and thus prevention of their development could actually accelerate the diseases process.