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Neurosci Lett. 2016 Apr 8;618:146-151. doi: 10.1016/j.neulet.2016.02.042. Epub 2016 Feb 24.

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

Author information

1
Division of Biomedical and Life Sciences, Faculty of Health and Medicine, University of Lancaster, Lancaster LA1 4AY, UK.
2
Manchester Pharmacy School, University of Manchester, Oxford Road, Manchester M13 9PT, UK. Electronic address: Harmesh.aojula@manchester.ac.uk.
3
Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK.

Abstract

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 α-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 α-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 α-synuclein is influenced by apoE concentration. At low concentrations of apoE (<15nM), all of the isoforms were able to increase the aggregation of α-synuclein (50μM), with apoE4 showing the greatest stimulatory effect. This is in contrast to a higher concentration (>15nM) of these isoforms, where a decrease in the aggregation of α-synuclein was noted. The data show that exceptionally low levels of apoE may seed α-syn aggregation, which could potentially lead to the pathogenesis of α-synuclein-induced neurodegeneration. On the other hand, higher levels of apoE could potentially lower the degree of α-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.

KEYWORDS:

Aggregation; Apolipoprotein E; Lewy body; Parkinson’s disease; α-Synuclein

PMID:
26921451
DOI:
10.1016/j.neulet.2016.02.042
[Indexed for MEDLINE]

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