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 and several cardiovascular disorders. We have a broad interest in the nature, pathogenesis and impact of a number of amyloid diseases, both systemic and localised.

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.

Neurodegenerative diseases

Cognitive impairment and dementia are common diseases that increase with age. It has been shown that a large proportion of individuals in their 80s exhibit neurodegenerative changes in the brain. In addition to the more well-known conditions, Alzheimer’s disease and Parkinson’s disease, new neurodegenerative diseases have been identified in recent years, such as Limbic-predominant Age-related TDP Encephalopathy.

Abnormal proteins lead to dementia

It has been demonstrated that in most neurodegenerative diseases, abnormal proteins such as beta-amyloid, hyperphosphorylated tau, alpha-synuclein, or transactive response DNA-binding protein 43 kDa, are present in the brain.

These proteins develop insidiously, increase in extent, and often display a prion-like spread to different regions of the brain, similar to that seen in amyloidosis-associated diseases. Over time, these pathologies lead to cognitive impairment and to dementia. What triggers the formation of these abnormal proteins remains unclear.

We study these proteins to identify the underlying mechanisms responsible for the initiation and progression of these incurable disease states.

The spread of amyloid diseases

Another of our areas of interest is the spread of amyloid diseases through a mechanism similar to the transmission of prions. Together with G.T. Westermark at the Department of Medical Cell Biology, we have used an experimental model of AA amyloidosis and seen that both naturally and non-naturally occurring forms of amyloid fibrils can cause disease.

Is AA amlyloid present in the environment?

In collaboration with researchers at SLU, we investigate the possibility that AA amyloid may be present in our environment and act as a risk factor for the onset of AA-amyloidosis in animals and humans. We are also interested in the origin and spread of age-related transthyretin amyloidosis.

Amyloid in other medical conditions

Local presence of amyloid has been shown to be important for Alzheimer's disease and type 2 diabetes, We areinvestigating the role of amyloid in other diseases, especially aortic aneurysms, atherosclerosis and certain heart valve conditions.

The presence of amyloid in atherosclerosis is an overlooked phenomenon, and we are currently evaluating a protein that could constitute an amyloid fibril in atherosclerosis.

Reference laboratory for amyloid diseases

We are part of the newly established Uppsala University Hospital Expert Centre for Diagnostics of Amyloidosis (ACAD), which, among other things, is intended to “serve as a centre of expertise, research, and education in systemic amyloidosis and promote integrated research between the hospital and the university.”

Our laboratory serves as a reference laboratory for diagnosing amyloid diseases and since 1 July 2024, it is part of national highly specialized care (NHV) of systemic amyloidosis at Uppsala University Hospital. The laboratory focuses on developing existing methods for determining the type of amyloidosis. For this reason, we are also developing new antibodies for use in clinical applications and are also applying mass spectroscopy.