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Publication
Morphological and Molecular Profiling of Amyloid-β Species in Alzheimer’s Pathogenesis
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Advisor(s)
Abstract(s)
Alzheimer’s disease (AD) is the most common form of dementia around the world (~ 65%). Here, we portray the neuropathology of AD, biomarkers, and classifcation of amyloid plaques (difuse, non-cored, dense core, compact). Tau pathology and its involvement with Aβ plaques and cell death are discussed. Amyloid cascade hypotheses, aggregation mechanisms, and molecular species formed in vitro and in vivo (on- and of-pathways) are described. Aβ42/Aβ40 monomers, dimers, trimers,
Aβ‐derived difusible ligands, globulomers, dodecamers, amylospheroids, amorphous aggregates, protofbrils, fbrils, and plaques are characterized (structure, size, morphology, solubility, toxicity, mechanistic steps). An update on AD-approved drugs by regulatory agencies, along with new Aβ-based therapies, is presented. Beyond prescribing Aβ plaque disruptors, cholinergic agonists, or NMDA receptor antagonists, other therapeutic strategies (RNAi, glutaminyl cyclase inhibitors, monoclonal antibodies, secretase modulators, Aβ aggregation inhibitors, and anti-amyloid vaccines) are already under clinical trials. New drug discovery approaches based on “designed multiple ligands”, “hybrid molecules”, or “multitarget-directed ligands” are also being put forward and may contribute to tackling this highly debilitating and fatal form of human dementia.
Description
Acknowledgements Authors acknowledge funding by COMPETE and
CENTRO-2020 and by Fundação para a Ciência e a Tecnologia (FCT).
Funding Open access funding provided by FCT|FCCN (b-on). Authors received funding from COMPETE and CENTRO-2020 and from Fundação para a Ciência e a Tecnologia (FCT): UIDB/00313/2020 and UIDP/00313/2020 (to Coimbra Chemistry Centre, University of Coimbra) and the doctoral fellowship SFRH/BD/137991/2018 (to Z.L.A.).
Funding Open access funding provided by FCT|FCCN (b-on). Authors received funding from COMPETE and CENTRO-2020 and from Fundação para a Ciência e a Tecnologia (FCT): UIDB/00313/2020 and UIDP/00313/2020 (to Coimbra Chemistry Centre, University of Coimbra) and the doctoral fellowship SFRH/BD/137991/2018 (to Z.L.A.).
Keywords
Alzheimer’s disease (AD) Amyloid-beta (Aβ) peptide Tau protein Protein aggregation Amyloid plaques Aβ-based therapies
Citation
Almeida, Z.L., Vaz, D.C. & Brito, R.M.M. Morphological and Molecular Profiling of Amyloid-β Species in Alzheimer’s Pathogenesis. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04543-4
Publisher
Springer Nature