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

被引：24

作者：

Mouchard, Amandine ^{[1
,2
]}

Boutonnet, Marie-Charlotte ^{[1
,2
]}

Mazzocco, Claire ^{[1
,2
]}

Biendon, Nathalie ^{[1
,2
]}

Macrez, Nathalie ^{[1
,2
]}

Letournel, Franck ^{[3
]}

Vital, Anne ^{[4
]}

Chapon, Francoise ^{[5
]}

Godfraind, Catherine ^{[6
]}

Maurage, Claude-Alain ^{[7
]}

Deramecourt, Vincent ^{[7
]}

Duchesne, Mathilde

Meyronnet, David ^{[8
]}

Streichenberger, Nathalie ^{[8
]}

de Paula, Andre Maues ^{[9
]}

Rigau, Valerie ^{[10
]}

Vandenbos-Burel, Fanny

Duyckaerts, Charles ^{[11
]}

Seilhean, Danielle ^{[12
]}

Sazdovitch, Veronique ^{[12
]}

Milin, Serge ^{[13
]}

Chiforeanu, Dan Christian ^{[14
]}

Laquerriere, Annie ^{[15
]}

Lannes, Beatrice ^{[16
]}

机构：

[1] Bordeaux Univ, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France

[2] CNRS, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France

[3] CHU Angers, Angers, France

[4] CHU Bordeaux, Bordeaux, France

[5] CHU Caen, Caen, France

[6] CHU Clermont Ferrand, Clermont Ferrand, France

[7] CHU Lille, Lille, France

[8] CHU Lyon, Lyon, France

[9] CHU Marseille, Marseille, France

[10] CHU Montpellier, Montpellier, France

[11] CHU PS Paris, Paris, France

[12] CHU PS, Paris, France

[13] CHU Poitiers, Poitiers, France

[14] CHU Rennes, Rennes, France

[15] CHU Rouen, Rouen, France

[16] CHU Strasbourg, Strasbourg, France

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

APOLIPOPROTEIN-E FRAGMENTS; AMYLOID-BETA; A-BETA; TYPE-4; ALLELE; PROTEIN; OLIGOMERS; PEPTIDE; RISK; ACCUMULATION; SUGGESTS;

D O I：

10.1038/s41598-019-40438-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Identification of endogenous pathological amyloid beta peptides (A beta) forms in the brains of patients with Alzheimer's disease (AD) is still unclear. In healthy brain, A beta 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 A beta and their interaction with the ApoE fragments in post-mortem brains from control and AD patients by western blots and co-immunoprecipitation. Three A beta-containing peptides and three ApoE fragments were specifically found in the brain of AD patients. Co-immunoprecipitations showed that ApoE fragments and A beta 1-42 peptides are co-partners in heteromers of 18 and 16 kDa while ApoE-fragments and A beta peptides of 12 kDa did not interact with each other. Formation of the 18 kDa ApoE-fragment/A beta heteromers is specifically increased in ApoE4 carriers and is a strong brain marker of AD while 16 kDa ApoE-fragment/A beta and A beta 12 kDa correlate to memory deficit. These data show that in patients with AD, ApoE fragmentation generates peptides that trap A beta in the brain. Inhibiting the fragmentation or targeting ApoE fragments could be exploited to define strategies to detect or reverse AD.

引用

页数：13