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ApoE protects cortical neurones against neurotoxicity induced by the non‐fibrillar C‐terminal domain of the amyloid‐β peptide
Author(s) -
Drouet Béatrice,
Fifre Alexandre,
PinçonRaymond Martine,
Vandekerckhove Joël,
Rosseneu Maryvonne,
Guéant JeanLouis,
Chambaz Jean,
Pillot Thierry
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00047.x
Subject(s) - neurotoxicity , apolipoprotein e , peptide , amyloid (mycology) , gene isoform , chemistry , microbiology and biotechnology , amyloid beta , biochemistry , biology , biophysics , toxicity , medicine , gene , disease , inorganic chemistry , organic chemistry
Although the genetic link between the ε4 allele of apolipoprotein E (apoE) and Alzheimer's disease (AD) is well established, the apoE isoform‐specific activity underlying this correlation remains unclear. We have recently characterized the interaction of the soluble the amyloid‐β peptide (Aβ) with model membrane and demonstrated that non‐fibrillar Aβ peptide, including N‐terminal truncated forms of Aβ, induced apoptotic cell death in primary rat cortical neurones in vitro . To further investigate the potential interaction between apoE and Aβ in the pathogenesis of AD, we have determined the effect of apoE isoforms on the neurotoxicity of non‐fibrillar Aβ peptides. We demonstrate here that the apoE2 and E3 isoforms protect cortical neurones against apoptotic cell death induced by a non‐fibrillar form of the Aβ 1−40 , Aβ 12−42 , Aβ 29−40 and Aβ 29−42 peptides, whereas apoE4 had no effect. This effect involves the formation of stable complexes between apoE and the C‐terminal domain (e.g. amino acids 29–40) of Aβ 1−40 . Interestingly, apoE had no effect on the toxicity induced by aggregated Aβ peptides, suggesting a lack of interaction between apoE and amyloid fibrils. Our results provide evidence that interaction with the C‐terminal domain of Aβ, apoE2 and E3, but not apoE4, inhibits the interactions of the non‐fibrillar Aβ peptide with the plasma membrane of neurones, Aβ peptide aggregation and subsequent neurotoxicity.