Possible biological function for the Alzheimer protein amyloid-beta

Published 2015-11-08 11:27. Updated 2015-11-23 13:28Denna sida på svenska
Senior Researcher Taher Darreh-Shori. Photo:Selma Wolofsky, Dept. of NVS, Karolinska Institutet.

A new study, conducted by researchers at Karolinska Institutet´s Department of Neurobiology, Care Sciences and Society (NVS), shows that amyloid-β-peptides, which are thought to be toxic and a suspected cause of Alzheimer’s disease, actually have a biological function.

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The discovery, which is published in the journal Brain, can help to explain why the so-called cholinergic signal systems are the first to be damaged on the onset of the disease.

Research on amyloid-β-peptides in Alzheimer’s disease has mainly been based on their presumed toxicity and causal role in the development of the disease. At the early stages of development, Alzheimer’s disease particularly affects cholinergic signalling via the neurotransmitter acetylcholine, but why this is the case is still unknown.

The present study indicates that amyloid-β has a physiological function and influences the balance of acetylcholine in the brain. What the researchers have discovered is that amyloid-β forms particular complexes that they call BAβAC (BChE/AChE/Aβ/ApoE complex). The complexes contain two different enzymes that break down acetylcholine at the synapses between nerve cells or between nerve cells and glial cells.

“When amyloid-β binds to them, the enzymes become hyperactive, and the neurotransmitter acetylcholine breaks down more rapidly,” says principal investigator, Dr Taher Darreh-Shori at NVS. “This could, in turn, change the functional status of the brain’s neuroglial cells, such as astrocytes and oligodendrocytes.”

The study

Amyloid-β peptides act as allosteric modulator of cholinergic signalling through formation of soluble BAβACs
Rajnish Kumar; Agneta Nordberg, Taher Darreh-Shori
BRAIN, first published online 2 November 2015, 
DOI: http://dx.doi.org/10.1093/brain/awv318 awv318 


Senior researcher

Taher Darreh-Shori

Phone: +46-(0)8-585 836 12
Organizational unit: Division of Translational Alzheimer Neurobiology
E-mail: Taher.Darreh-Shori@ki.se