New Protein Discovery Could Be Used to Diagnose Alzheimer's Disease

Researchers have discovered a previously unknown substance in spinal fluid that could be used to diagnose Alzheimer's disease.

The substance is a beta-amyloid protein called Abeta16. Two independent studies have shown that Alzheimer's patients have higher levels of the protein in their spinal fluid than do healthy individuals.

'The discovery of the new protein could be used to diagnose patients with Alzheimer's disease, says biochemist Erik Portelius, the author of the thesis in which the study results are published.

Alzheimer’s disease is an age-related progressive neurodegenerative disorder of the central nervous system. Diagnosis and monitoring of sporadic Alzheimer’s disease has long depended on clinical examination of individuals with end-stage disease.

The accumulation of amyloid-β peptides in specific brain regions is believed to represent the earliest event in the pathogenesis of Alzheimer’s disease and there is developing consensus for the use of cerebrospinal fluid as a core biomarker for the mild cognitive impairment stage of Alzheimer’s disease.

Alzheimer's disease includes the formation of plaque on the brain. Neurons and other cell types form around 20 different beta-amyloid proteins, and these are excreted into the spinal fluid around the brain.

'These types of beta-amyloid proteins can be analyzed with great precision, and our research team has also shown that the analyses can be used to distinguish between Alzheimer's patients and healthy individuals with a high degree of accuracy', says Portelius.

The beta-amyloid protein Abeta42 is particularly prevalent in the plaque. Abeta42 is created when a larger protein is cut into pieces by certain enzymes. Alzheimer's drugs that are currently being tested aim to reduce the production of Abeta42 by blocking these enzymes. Portelius found that these drugs increase the level of the newly discovered Abeta16.

’Abeta42 and Abeta16 are formed from the same precursor molecule, but the enzymatic process is different and Abeta16 is not harmful. The finding that Abeta16 is a very sensitive biomarker for the effect of these drugs may become very useful in future treatment studies', says Portelius.

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References:
1. Erik Portelius. Targeted Abeta proteomics – A tool to study the pathogenesis of Alzheimer’s disease. Institute of Neuroscience and Physiology. Department of Psychiatry and Neurochemistry, University of Gothenburg. http://hdl.handle.net/2077/20444.