Send to

Choose Destination
J Biol Chem. 2006 Sep 22;281(38):27916-23. Epub 2006 Jul 26.

Acceleration of amyloid beta-peptide aggregation by physiological concentrations of calcium.

Author information

Department of Neurology and Division of Neuroscience, The Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.


Alzheimer disease is characterized by the accumulation of aggregated amyloid beta-peptide (Abeta) in the brain. The physiological mechanisms and factors that predispose to Abeta aggregation and deposition are not well understood. In this report, we show that calcium can predispose to Abeta aggregation and fibril formation. Calcium increased the aggregation of early forming protofibrillar structures and markedly increased conversion of protofibrils to mature amyloid fibrils. This occurred at levels 20-fold below the calcium concentration in the extracellular space of the brain, the site at which amyloid plaque deposition occurs. In the absence of calcium, protofibrils can remain stable in vitro for several days. Using this approach, we directly compared the neurotoxicity of protofibrils and mature amyloid fibrils and demonstrate that both species are inherently toxic to neurons in culture. Thus, calcium may be an important predisposing factor for Abeta aggregation and toxicity. The high extracellular concentration of calcium in the brain, together with impaired intraneuronal calcium regulation in the aging brain and Alzheimer disease, may play an important role in the onset of amyloid-related pathology.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center