Nigral burden of alpha-synuclein correlates with striatal dopamine deficit

Abstract

Aggregated alpha-synuclein is the hallmark of Parkinson's disease (PD), diffuse Lewy body disease (DLBD), and multiple system atrophy (MSA). Physiologically, alpha-synuclein ensures normal functions of dopamine transporter (DAT) and tyrosine hydoxylase. In alpha-synucleinopathies, it accumulates in neuronal cytoplasm and neurites through several stages. It is unclear whether the accumulation of pathological alpha-synuclein in the substantia nigra in PD correlates with the dopaminergic deficit in the striatal target. We evaluated the impact of the nigral burden of pathological alpha-synuclein immunoreactivity in 27 alpha-synucleinopathy brains by morphometric immunohistochemistry. DAT immunoreactivity in the striatum inversely correlates with the total alpha-synuclein burden in the substantia nigra but not with cytoplasmic inclusion counts only. This result has implications for imaging, clinicopathological correlative studies, and staging of the disease process.