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Aβ Toxicity in Alzheimer's Disease

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Abstract

Alzheimer's Disease (AD), the most common age-related neurodegenerative disorder, is characterized by progressive cognitive decline, synaptic loss, the formation of extracellular β-amyloid plaques and intracellular neurofibrillary tangles, and neuronal cell death. Despite the massive neuronal loss in the ‘late stage’ of disease, dendritic spine loss represents the best pathological correlate to the cognitive impairment in AD patients. The ‘amyloid hypothesis’ of AD recognizes the Aβ peptide as the principal player in the pathological process. Many lines of evidence point out to the neurotoxicity of Aβ, highlighting the correlation between soluble Aβ oligomer accumulation, rather than insoluble Aβ fibrils and disease progression. Pathological increase of Aβ in AD brains, resulting from an imbalance between its production, aggregation and clearance, might target mitochondrial function promoting a progressive synaptic impairment. The knowledge of the exact mechanisms by which Aβ peptide impairs neuronal function will help us to design new pharmacological tools for preventing AD neurodegeneration.

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Acknowledgments

MDA is financially supported by PRIN 2009 (Projects for Research of National Interest) and by a grant from the Alzheimer's Association (NIRG-11-204588). FC is supported by the Telethon Foundation, the Italian Ministry of Health and the Italian Ministry of Research, through Ricerca Finalizzata, Ricerca Corrente and FIRB funds.

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Authors and Affiliations

  1. Department of Experimental Neurosciences, IRCCS Fondazione Santa Lucia, 00143, Rome, Italy

    Virve Cavallucci, Marcello D’Amelio & Francesco Cecconi

  2. University Campus-Biomedico, 00128, Rome, Italy

    Marcello D’Amelio

  3. Dulbecco Telethon Institute at the Department of Biology, University of Rome Tor Vergata, 00133, Rome, Italy

    Francesco Cecconi

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  1. Virve Cavallucci
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  2. Marcello D’Amelio
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  3. Francesco Cecconi
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Correspondence to Francesco Cecconi.

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Cavallucci, V., D’Amelio, M. & Cecconi, F. Aβ Toxicity in Alzheimer's Disease. Mol Neurobiol 45, 366–378 (2012). https://doi.org/10.1007/s12035-012-8251-3

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