Molecular subtypes of Alzheimer's disease

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number3269
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Alzheimer Disease
Amyloid
Brain
Amyloidosis
Phenotype
Peptides
Aptitude
Neurodegenerative Diseases
Blood Vessels
Seeds
Peptide Hydrolases
Animal Models
Proteins

ASJC Scopus subject areas

  • General

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Molecular subtypes of Alzheimer's disease. / Di Fede, Giuseppe; Catania, Marcella; Maderna, Emanuela; Ghidoni, Roberta; Benussi, Luisa; Tonoli, Elisa; Giaccone, Giorgio; Moda, Fabio; Paterlini, Anna; Campagnani, Ilaria; Sorrentino, Stefano; Colombo, Laura; Kubis, Adriana; Bistaffa, Edoardo; Ghetti, Bernardino; Tagliavini, Fabrizio.

In: Scientific Reports, Vol. 8, No. 1, 3269, 01.12.2018.

Research output: Contribution to journalArticle

Di Fede, G, Catania, M, Maderna, E, Ghidoni, R, Benussi, L, Tonoli, E, Giaccone, G, Moda, F, Paterlini, A, Campagnani, I, Sorrentino, S, Colombo, L, Kubis, A, Bistaffa, E, Ghetti, B & Tagliavini, F 2018, 'Molecular subtypes of Alzheimer's disease', Scientific Reports, vol. 8, no. 1, 3269. https://doi.org/10.1038/s41598-018-21641-1
Di Fede, Giuseppe ; Catania, Marcella ; Maderna, Emanuela ; Ghidoni, Roberta ; Benussi, Luisa ; Tonoli, Elisa ; Giaccone, Giorgio ; Moda, Fabio ; Paterlini, Anna ; Campagnani, Ilaria ; Sorrentino, Stefano ; Colombo, Laura ; Kubis, Adriana ; Bistaffa, Edoardo ; Ghetti, Bernardino ; Tagliavini, Fabrizio. / Molecular subtypes of Alzheimer's disease. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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