MedicalResearch.com Interview with: Prof. Konstantinos Stellos, MD, DM, MRCP, DSc, FAHA, FESC Professor of Medicine, Chair of Cardiovascular Medicine, Chair of Epitranscriptomics Lead, Vascular Biology & Medicine Theme Hon. Consultant Cardiologist, Newcastle Hospitals NHS Foundation Trust Biosciences Institute Faculty of Medical Sciences Newcastle University MedicalResearch.com: What is the background for this seminar? Can you tell us a little about how amyloid is made and stored? Response: Patients are afraid that they may die due to a heart attack - a major cause of death worldwide- or if they live long they may get dementia compromising severely their quality of life in their last years of life. Many years ago we asked the question whether there is a link between these two ageing-associated diseases. For this reason we studied the clinical value of amyloid-beta peptides in patients with coronary heart disease. We chose to study the amyloid-beta peptides, which are the cleavage product of the beta- and gamma-secretases of the mother protein amyloid precursor protein, because amyloid-beta plaques in brain is the hallmark of Alzheimer's disease. Following amyloid precursor protein (APP) gene transcription, APP is cleaved in the nonamyloidogenic pathway (plasma membrane) by α- and γ- secretases or in the amyloidogenic pathway (endosomes) by β- and γ- secretases. The later pathway generates amyloid beta (Αβ) peptides that are released extracellularly. Αβ accumulation in blood or tissues may result from enhanced production/cleavage or by impaired degradation and/or clearance. The related mechanisms are depicted in Figure 2 of our publication in JACC: http://www.onlinejacc.org/content/75/8/952  (more…)