Aβ toxicity in Alzheimer's disease

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)366-378
Number of pages13
JournalMolecular Neurobiology
Volume45
Issue number2
DOIs
Publication statusPublished - Apr 2012

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Keywords

  • APP
  • Early AD
  • Glutamatergic transmission
  • Mitochondria
  • Synapse loss
  • Synaptic plasticity

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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