Abstract
Amyloid-beta (Aβ) peptide oligomers are believed to be the causative agents of Alzheimer's disease (AD). Though post-mortem examination shows that insoluble fibrils are deposited in the brains of AD patients in the form of intracellular (tangles) and extracellular (plaques) deposits, it has been observed that cognitive impairment is linked to synaptic dysfunction in the stages of the illness well before the appearance of these mature deposits. Increasing evidence suggests that the most toxic forms of Aβ are soluble low-oligomer ligands whose amounts better correlate with the extent of cognitive loss in patients than the amounts of fibrillar insoluble forms. Therefore, these ligands hold the key to a better understanding of AD prompting the search for clearer correlations between their structure and toxicity. The importance of such correlations and their diagnostic value for the early diagnosis of AD is discussed here with a particular emphasis on the transient nature and structural plasticity of misfolded Aβ oligomers.
Highlights
Reviewed by: Luis Álvarez De Cienfuegos Rodríguez, University of Granada, Spain Juan Jose Diaz-Mochon, University of Granada, Spain Richard B
Though post-mortem examination shows that insoluble fibrils are deposited in the brains of Alzheimer’s disease (AD) patients in the form of intracellular and extracellular deposits, it has been observed that cognitive impairment is linked to synaptic dysfunction in the stages of the illness well before the appearance of these mature deposits
Cerebral proteopathies including Alzheimer’s, Parkinson’s, and Huntington’s diseases result from progressive amyloidogenesis for which protein misfolding is the cause (Eisenberg and Jucker, 2012).The complexity of these diseases is the main reason behind the persistent lack of efficient therapeutic approaches
Summary
Reviewed by: Luis Álvarez De Cienfuegos Rodríguez, University of Granada, Spain Juan Jose Diaz-Mochon, University of Granada, Spain Richard B. Specialty section: This article was submitted to Medicinal and Pharmaceutical Chemistry, a section of the journal
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