New biomarker of Alzheimer's disease
A group of scientists from the SBP Medical Research Institute (Sanford Burnham Prebys Medical Discovery Institute), California, have identified a cyclic peptide (DAG) that can be used to diagnose Alzheimer's disease at an early stage.
DAG peptide (green) on a vessel (red) in the hippocampus of a mouse brain with an Alzheimer's disease model. Source: Ruoslahti Lab, SBP.
This peptide is able to recognize connective tissue growth factor (CTGF), which appears in the blood vessels of the brain of mice with Alzheimer's disease. It is noteworthy that CTGF is detected in the blood before the appearance of amyloid plaques – today the main pathogenetic marker of Alzheimer's disease.
CTGF protein is produced in brain cells in response to inflammation and tissue healing processes. Its detection is confirmed by the results of recent studies, according to which, the leading mechanism of Alzheimer's disease is inflammation.
Detection of the DAG peptide was performed in vivo in the hippocampus of mice using a phage display at different stages of Alzheimer's disease.
The peptide was detected in the brain vessels of mice at an early stage of the disease. If the same data are available in humans, then it will be possible to make a big step forward in the diagnosis and therapy of Alzheimer's disease: treatment initiated at an early, asymptomatic stage will probably be able to improve the prognosis of the disease.
Another important point: in the presence of CTGF protein, the DAG peptide is able to bind to endothelial cells. This proves that the endothelial cells lining the blood vessels of the brain from the inside are also involved in the inflammatory process in Alzheimer's disease. The significance of this observation is very high: unlike brain cells, which are poorly accessible due to the hemato-encephalic barrier, endothelial cells are easily accessible for therapeutic and diagnostic drugs.
Now the authors of the article intend to develop a method for diagnosing Alzheimer's disease in mice using magnetic resonance imaging or positron emission tomography. According to them, as soon as results are obtained in this direction, they will study the early stage of the disease in humans.
The CTGF protein will also help develop targeted therapy for Alzheimer's disease. Given the huge number of unsuccessful studies of treatment methods at the stage of detection of beta-amyloid (a toxic protein involved in the formation of plaques in the brain), a new direction focused on earlier diagnosis and timely treatment may have great potential.
The authors do not exclude that the CTGF protein may also appear in other brain diseases associated with inflammation. Thus, its detailed study can lead to new discoveries in the treatment of neurological diseases.
Article by Aman P. Mann et al. Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer's disease is published in the journal Nature.