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Updated: May 25, 2026

Enrichment of Detergent-insoluble Protein Aggregates from Human Postmortem Brain
Published on: October 24, 2017
Granular non-fibrillar aggregates and toxicity in Alzheimer's disease
Núria Benseny-Cases1, Oxana Klementieva, Jan Malý
1Biophysics Unit and Centre of Studies in Biophysics, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia, Spain.
Abstract:
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.
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