ApoE-fragment/Aβ heteromers in the brain of patients with Alzheimer’s disease.

Amandine Mouchard, , Marie-Charlotte Boutonnet, Claire Mazzocco, Nathalie Biendon, Nathalie Macrez
Sci Rep. 2019-03-08; 9(1):
DOI: 10.1038/s41598-019-40438-4

PubMed
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1. Sci Rep. 2019 Mar 8;9(1):3989. doi: 10.1038/s41598-019-40438-4.

ApoE-fragment/Aβ heteromers in the brain of patients with Alzheimer’s disease.

Mouchard A(1)(2), Boutonnet MC(1)(2), Mazzocco C(1)(2), Biendon N(1)(2), Macrez
N(3)(4); Neuro-CEB Neuropathology Network.

Author information:
(1)Bordeaux University, Institut des Maladies Neurodégénératives, UMR, 5293,
Bordeaux, France.
(2)CNRS, Institut des Maladies Neurodégénératives, UMR, 5293, Bordeaux, France.
(3)Bordeaux University, Institut des Maladies Neurodégénératives, UMR, 5293,
Bordeaux, France. .
(4)CNRS, Institut des Maladies Neurodégénératives, UMR, 5293, Bordeaux, France.
.

Identification of endogenous pathological amyloid β peptides (Aβ) forms in the
brains of patients with Alzheimer’s disease (AD) is still unclear. In healthy
brain, Aβ can associate with Apolipoprotein E (ApoE) which is involved in its
metabolism and clearance. In the brain of patients with AD, ApoE is cleaved and
produces ApoE fragments. We studied the forms of Aβ and their interaction with
the ApoE fragments in post-mortem brains from control and AD patients by western
blots and co-immunoprecipitation. Three Aβ-containing peptides and three ApoE
fragments were specifically found in the brain of AD patients.
Co-immunoprecipitations showed that ApoE fragments and Aβ1-42 peptides are
co-partners in heteromers of 18 and 16 kDa while ApoE-fragments and Aβ peptides
of 12 kDa did not interact with each other. Formation of the 18 kDa
ApoE-fragment/Aβ heteromers is specifically increased in ApoE4 carriers and is a
strong brain marker of AD while 16 kDa ApoE-fragment/Aβ and Aβ 12 kDa correlate
to memory deficit. These data show that in patients with AD, ApoE fragmentation
generates peptides that trap Aβ in the brain. Inhibiting the fragmentation or
targeting ApoE fragments could be exploited to define strategies to detect or
reverse AD.

DOI: 10.1038/s41598-019-40438-4
PMCID: PMC6408522
PMID: 30850702 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus