Granular non-fibrillar aggregates and toxicity in Alzheimer's disease

Núria Benseny-Cases, Oxana Klementieva, Jan Malý, Josep Cladera*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)


Granular non-fibrillar aggregates (GNAs) are identified as possible toxic species in Alzheimer's disease. GNAs form on the surface of negatively charged biological membranes and as a consequence of an acidic environment, off the polymerization pathway at neutral pH. Aβ (1-40) GNAs disturb the bilayer structure of model membranes and seem to be more toxic to cells with negatively charged membranes (consequence of chronic pre-apoptosis). GNAs may be relevant in physiological situations associated to Alzheimer's disease: a local acidic pH at the cell surface (consequence of lipid oxidation or other cell insults) and acidification as a consequence of vascular events causing hypoxia. Together with previous descriptions of granular aggregates with poly-glutamine peptides related to Huntington's disease and the SH3 domain of PI3, GNAs related to Alzheimer's disease are a further example of a possible common aggregation and toxicity mechanism in conformational diseases. GNAs may represent a new pharmacological target in Alzheimer's disease. © 2012 Bentham Science Publishers.
Original languageEnglish
Pages (from-to)962-971
JournalCurrent Alzheimer Research
Issue number8
Publication statusPublished - 26 Oct 2012


  • Alzheimer's
  • Amyloid
  • Membranes
  • Non-fibrillar
  • PH


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