Nigral burden of alpha-synuclein correlates with striatal dopamine deficit.
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.
Kovacs
Gabor G
GG
Institute of Neurology, Medical University of Vienna, Austria.
Milenkovic
Ivan J
IJ
Preusser
Matthias
M
Budka
Herbert
H
D000368:Aged; D000369:Aged, 80 and over; D004298:Dopamine / Q000172:deficiency*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000473:pathology*; D011180:Postmortem Changes; D013378:Substantia Nigra / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D051844:alpha-Synuclein; D004298:Dopamine