Per Westermark – Amyloid research

The assembly of proteins into amyloid fibrils as cause of disease is attracting increasing attention, not only in systemic disorders and in connection with neurodegenerative conditions but also associated with other diseases such as type 2 diabetes. We have a broad interest in the nature, pathogenesis and impact of a number of amyloid diseases, both systemic and localized.

Together with researchers in Umeå we have found that there are two distinct phenotypes in Swedish familial transthyretin (TTR)-derived amyloidosis and that these are characterized by differences in posttranslational processing of the protein. We can distinguish between the two with the aid of a simple subcutaneous adipose tissue biopsy. This is important since one of the phenotypes carries a big risk of progressive cardiomyopathy also after liver transplantation, which is the main treatment today.

While the Swedish type of mutation (V30M) is characterized by the two different phenotypes, most other TTR mutations have the phenotype associated with a risk for cardiomyopathy. We have recently shown that spinal stenosis may be a manifestation of TTR-amyloidosis, both of wildtype and of mutation-associated type. A prospective study involving 130 patients, undergoing surgery for lumbar spinal stenosis is ongoing. Removed tissue is examined for presence of TTR amyloid. Those patients with such deposits are invited to cardiologic investigation with echocardiography, MRI and other methods.

Transmission of amyloid diseases

The possible transmission of amyloid diseases by a prion-like mechanism is one of our main interests. We are, in collaboration with researchers at SVL and SLU, Uppsala, performing studies on the possibility that AA-amyloid may be present in our environment including our food and act a putative risk factor for development of the disease in animals and human. Together with G.T. Westermark, Department of Medical Cell Biology, we have found that seeding, cross-seeding and transmission of localized amyloidoses are possible, such as those consisting of Aβ and IAPP.

Amyloids in other diseases

Localized amyloid has been identified as important actors in Alzheimer’s disease and type 2 diabetes. We are currently investigating the possibility that amyloid deposits also are important in some other major diseases, particularly aortic aneurysm and atherosclerosis. Amyloid in atherosclerotic plaques is an overlooked phenomenon and our hypothesis is that toxic protein aggregates are mechanistic in the pathogenesis of atherosclerotic lesions. We are evaluating a candidate protein for the atherosclerotic amyloid fibril.  

Reference laboratory for amyloid diagnostics

Our laboratory is also working in association with the University Hospital and is performing amyloid diagnostic work within the hospital. As systemic amyloidoses are increasingly identified as clinical problems particularly in elderly, we are receiving an increasing number of biopsies each year. Our laboratory is devoted to further develop existing methods to determine type of systemic amyloidosis. For this, we are also developing new antibodies for clinical use and are planning to introduce mass spectrometry.