Effects of different isoforms of apoE on aggregation of the α-synuclein protein implicated in Parkinson's disease

Parkinson's disease is a progressive brain disorder due to the degeneration of dopaminergic neurons in the substantia nigra. The accumulation of aggregated forms of alpha-synuclein protein into Lewy bodies is one of the characteristic features of this disease although the pathological role of any such protein deposits in causing neurodegeneration remains elusive. Here, the effects of different apolipoprotein E isoforms (apoE2, apoE3, apoE4) on the aggregation of alpha-synuclein in vitro were examined using thioflavin T assays and also an immunoassay to detect the formation of multimeric forms. Our results revealed that the aggregation of alpha-synuclein is influenced by apoE concentration. At low concentrations of apoE (<15 nM), all of the isoforms were able to increase the aggregation of alpha-synuclein (50 mu M), with apoE4 showing the greatest stimulatory effect. This is in contrast to a higher concentration (>15 nM) of these isoforms, where a decrease in the aggregation of alpha-synuclein was noted. The data show that exceptionally low levels of apoE may seed alpha-syn aggregation, which could potentially lead to the pathogenesis of alpha-synucleini-nduced neurodegeneration. On the other hand, higher levels of apoE could potentially lower the degree of alpha-synuclein aggregation and confer protection. The differential effects noted with apoE4 could explain why this particular isoform results in an earlier age of onset for Parkinson's disease. (C) 2016 Elsevier Ireland Ltd. All rights reserved.