Oligomeric Pyroglutamate Amyloid-β is Present in Microglia and a Subfraction of Vessels in Patients with Alzheimer's Disease: Implications for Immunotherapy

被引：17

作者：

Wirths, Oliver ^{[1
]}

Hillmann, Antje ^{[1
]}

Pradier, Laurent ^{[2
]}

Haertig, Wolfgang ^{[3
]}

Bayer, Thomas A. ^{[1
]}

机构：

[1] Univ Med Goettingen, Univ Gottingen, Div Mol Psychiat, D-37075 Gottingen, Germany

[2] Sanofi Aventis, Therapeut Strategy Unit Aging, Chilly Mazarin, France

[3] Univ Leipzig, Paul Flechsig Inst Brain Res, Fac Med, D-04109 Leipzig, Germany

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2013年 / 35卷 / 04期

关键词：

9D5; Alzheimer's disease; amyloid; APP/PS1KI transgenic mouse model; gliosis; microglia; pyroglutamate A beta; rhesus monkey; PEPTIDES IN-VITRO; A-BETA; PRECURSOR PROTEIN; TRANSGENIC MICE; ANIMAL-MODEL; MOUSE MODEL; ANGIOPATHY; AGGREGATION; PLAQUES; BRAIN;

D O I：

10.3233/JAD-121945

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

N-terminally truncated pyroglutamate amyloid-beta (A beta) starting at position 3 (A beta pE3) represents a major fraction of A beta peptides in Alzheimer's disease (AD). Recently, we have identified low molecular weight A beta(pE3) oligomers, which can be detected by 9D5, a novel mouse monoclonal antibody. In the present study, we analyzed the immunohistochemical staining profile in the brain of patients with AD and in the APP/PS1KI mouse model, as well as in aged rhesus monkeys. 9D5-positive microglia and blood vessels were found in many AD cases, in the transgenic mouse model, and in an aged macaque. The presence of 9D5-immunoreactivity in microglia indicates that low molecular weight A beta(pE3) oligomers may be phagocytosed, since in the APP/ PS1KI model, A beta is exclusively produced in neurons due to neuronal expression of transgenic A beta PP.

引用

页码：741 / 749

页数：9

共 42 条

[1] Permanent middle cerebral artery occlusion in sheep: a novel large animal model of focal cerebral ischemia [J].

Boltze, Johannes ;

Foerschler, Annette ;

Nitzsche, Bjoern ;

Waldmin, Daniela ;

Hoffmann, Anke ;

Boltze, Christiane M. ;

Dreyer, Antje Y. ;

Goldammer, Axel ;

Reischauer, Anne ;

Haertig, Wolfgang ;

Geiger, Kathrin D. ;

Barthel, Henryk ;

Emmrich, Frank ;

Gille, Uwe .

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2008, 28 (12) :1951-1964

[2] Mechanisms of cerebrovascular amyloid deposition - Lessons from mouse models [J].

Burgermeister, P ;

Calhoun, ME ;

Winkler, DT ;

Jucker, M .

VASCULAR FACTORS IN ALZHEIMER'S DISEASE, 2000, 903 :307-316

[3] Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology [J].

Carare, R. O. ;

Bernardes-Silva, M. ;

Newman, T. A. ;

Page, A. M. ;

Nicoll, J. A. R. ;

Perry, V. H. ;

Weller, R. O. .

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2008, 34 (02) :131-144

[4] Massive CA1/2 neuronal loss with intraneuronal and N-interminal truncated Aβ42 accumulation in a novel Alzheimer transgenic model [J].

Casas, C ;

Sergeant, N ;

Itier, JM ;

Blanchard, V ;

Wirths, O ;

van der Kolk, N ;

Vingtdeux, V ;

van de Steeg, E ;

Ret, G ;

Canton, T ;

Drobecq, H ;

Clark, A ;

Bonici, B ;

Delacourte, A ;

Benavides, J ;

Schmitz, C ;

Tremp, G ;

Bayer, TA ;

Benoit, P ;

Pradier, L .

AMERICAN JOURNAL OF PATHOLOGY, 2004, 165 (04) :1289-1300

[5] Activation of toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid β peptide [J].

Chen, KQ ;

Iribarren, P ;

Hu, JY ;

Chen, JH ;

Gong, WH ;

Cho, EH ;

Lockett, S ;

Dunlop, NM ;

Wang, JM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (06) :3651-3659

[6] N-Terminal Truncated Pyroglutamyl β Amyloid Peptide Aβpy3-42 Shows a Faster Aggregation Kinetics than the Full-Length Aβ1-42 [J].

D'Arrigo, Cristina ;

Tabaton, Massimo ;

Perico, Angelo .

BIOPOLYMERS, 2009, 91 (10) :861-873

[7]

Geddes JW, 1999, NEUROBIOL AGING, V20, P75

[8] ALZHEIMERS-DISEASE - INITIAL REPORT OF THE PURIFICATION AND CHARACTERIZATION OF A NOVEL CEREBROVASCULAR AMYLOID PROTEIN [J].

GLENNER, GG ;

WONG, CW .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 120 (03) :885-890

[9] Concomitant detection of β-amyloid peptides with N-terminal truncation and different C-terminal endings in cortical plaques from cases with Alzheimer's disease, senile monkeys and triple transgenic mice [J].

Haertig, Wolfgang ;

Goldhammer, Simone ;

Bauer, Ute ;

Wegner, Florian ;

Wirths, Oliver ;

Bayer, Thomas A. ;

Grosche, Jens .

JOURNAL OF CHEMICAL NEUROANATOMY, 2010, 40 (01) :82-92

[10] The Aβ 3-pyroglutamyl and 11-pyroglutamyl peptides found in senile plaque have greater β-sheet forming and aggregation propensities in vitro than full-length Aβ [J].

He, WL ;

Barrow, CJ .

BIOCHEMISTRY, 1999, 38 (33) :10871-10877

← 1 2 3 4 5 →