RETRACTED: In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus (Retracted Article)

被引:6
|
作者
Benseny-Cases, Nuria [1 ]
Alvarez-Marimon, Elena [2 ,3 ]
Aso, Ester [4 ]
Carmona, Margarita [4 ]
Klementieva, Oxana [5 ]
Appelhans, Dietmar [6 ]
Ferrer, Isidre [4 ]
Cladera, Josep [2 ,3 ]
机构
[1] ALBA Synchrotron Light Source, Carrer De La Llum 2-26, Cerdanyola Del Valles 08290, Catalonia, Spain
[2] Univ Autonoma Barcelona, Fac Med, Unitat Biofis, Bellaterra 08193, Catalonia, Spain
[3] Univ Autonoma Barcelona, Ctr Estudis Biofis, Dept Bioquim & Biol Mol, Fac Med, Bellaterra 08193, Catalonia, Spain
[4] Univ Barcelona, Biomed Network Res Ctr Neurodegenerat Dis CIBERNE, Hosp Llobregat, Catalonia 08907, Spain
[5] Lund Univ, Dept Expt Med Sci, Med Microspect Res Grp, S-22180 Lund, Sweden
[6] Leibniz Inst Polymer Res Dresden, Hohe Str 6, D-01069 Dresden, Free State Of S, Germany
关键词
MICROSPECTROSCOPY MU-FTIR; BETA-SHEET; A-BETA; NATURAL MODEL; OLIGOMERS; TISSUE; BRAIN;
D O I
10.1038/s41598-020-62708-2
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
Amyloid plaques composed of A beta amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer's disease. In situ identification of early-stage amyloid aggregates in Alzheimer's disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice and Octodon degus for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months whereas very little formation of fibrils is found in aged Octodon degus. Finally, significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with G4-His-Mal dendrimers (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating putative therapeutic properties of G4-His-Mal dendrimers in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques.
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页数:10
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