Molecular subtypes of Alzheimer’s disease

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作者
Giuseppe Di Fede
Marcella Catania
Emanuela Maderna
Roberta Ghidoni
Luisa Benussi
Elisa Tonoli
Giorgio Giaccone
Fabio Moda
Anna Paterlini
Ilaria Campagnani
Stefano Sorrentino
Laura Colombo
Adriana Kubis
Edoardo Bistaffa
Bernardino Ghetti
Fabrizio Tagliavini
机构
[1] IRCCS Foundation “Carlo Besta” Neurological Institute,Department of Molecular Biochemistry and Pharmacology
[2] Molecular Markers Laboratory,Department of Toxicology
[3] IRCCS Istituto Centro San Giovanni di Dio - Fatebenefratelli,Department of Pathology and Laboratory Medicine
[4] IRCCS Istituto di Ricerche Farmacologiche “Mario Negri”,undefined
[5] Wroclaw Medical University,undefined
[6] Indiana University,undefined
[7] Indianapolis,undefined
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Scientific Reports | / 8卷
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摘要
Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer’s disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the brain in the form of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is characterized by distinct clinical and neuropathological phenotypes. Recent studies revealed that Aβ assemblies might have structural differences among AD brains and that such pleomorphic assemblies can correlate with distinct disease phenotypes. We found that in both sporadic and inherited forms of AD, amyloid aggregates differ in the biochemical composition of Aβ species. These differences affect the physicochemical properties of Aβ assemblies including aggregation kinetics, resistance to degradation by proteases and seeding ability. Aβ-amyloidosis can be induced and propagated in animal models by inoculation of brain extracts containing aggregated Aβ. We found that brain homogenates from AD patients with different molecular profiles of Aβ are able to induce distinct patterns of Aβ-amyloidosis when injected into mice. Overall these data suggest that the assembly of mixtures of Aβ peptides into different Aβ seeds leads to the formation of distinct subtypes of amyloid having distinctive physicochemical and biological properties which result in the generation of distinct AD molecular subgroups.
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