There is some evidence for the deposition of misfolded proteins into solid structures known as amyloid to contribute to the development of arthritis. Amyloid is better known for its role in Alzheimer's disease, but there are a number of types of amyloid, each a different misfolded protein, and for many of these the the relationships to age-related disease are still tentative or only partially explored. In recent years transthyretin amyloid has been recognized as important in heart disease and a range of other conditions, for example, but these are quite new discoveries despite the fact that the existence of this type of amyloid has been recognized for a long time. Still, amyloids are one of the characteristic differences between old tissue and young tissue: the research community should be aiming at the development of safe methods of removal for all of them, even in advance of a comprehensive understanding of how exactly they cause harm.
Amyloidosis is a protein conformational disorder in which amyloid fibrils accumulate in the extracellular space and induce organ dysfunction. Recently, two different amyloidogenic proteins, transthyretin (TTR) and apolipoprotein A-I (Apo A-I), were identified in amyloid deposits in knee joints in patients with knee osteoarthritis (OA). However, clinicopathological differences related to those two kinds of amyloid deposits in the knee joint remain to be clarified. Here, we investigated the clinicopathological features related to these knee amyloid deposits associated with knee OA and the biochemical characteristics of the amyloid deposits.
We found that all of our patients with knee OA had amyloid deposits in the knee joints, especially in the meniscus, and those deposits were primarily derived from TTR and/or Apo A-I. Some patients with knee OA, however, had unclassified amyloid deposits. One of our interesting observations concerned the different effects of aging on each type of amyloid formed. The frequency of formation of ATTR deposits clearly increased with age, but that of AApo A-I deposits decreased. Furthermore, we found that ∼16% of patients with knee OA developed ATTR/AApo A-I double deposits in the meniscus. Amyloid deposition may therefore be a common histopathological feature associated with knee OA. Also, aging may induce ATTR formation in the knee joint in elderly patients with knee OA, whereas AApo A-I formation may be inversely correlated with age.