Knee osteoarthritis associated with different kinds of amyloid deposits and the impact of aging on type of amyloid

Abstract

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.

Amyloid Proteins and Peripheral Neuropathy

“…For example, in sural nerve biopsies of rheumatoid arthritis patients, perineurial thickening with amyloid was detected in 4 out of 23 patients investigated [ 163 ]. In knee joints of 12 out of 12 osteoarthritis patients, as well as 7 out of 12 aged individuals without osteoarthritis, amyloid was present in menisci, articular cartilage, and synovial membranes, mostly of TTR and Apo-AI origin [ 164 , 165 ]. In psoriatic arthritis, amyloid has been reported in 30 cases and was present mainly in the kidney [ 166 ].…”

Effects of sporadic transthyretin amyloidosis frequently on the gallbladder and the correlation between amyloid deposition in the gallbladder and heart

“…Ligament involvement is extremely common in ATTRwt amyloidosis 23,24,30,31 . In particular, CTS has been reported as the most common initial symptom, and patients may present with symptoms of CTS 5-15 years prior to cardiac impairment 23 .…”

“…The second possibility is that ATTR deposition is affected by the presence or absence of degeneration and in ammation. Because previous reports evaluated surgical materials obtained from symptomatic sites, degeneration and in ammation should be present 24,30,31 . Conversely, we evaluated the ligaments with no observed in ammation and degeneration, and thus, amyloid deposition might have been missed.…”

Apolipoprotein A‐I: the dual face of a protein

“…The first analysis of amyloid deposit composition in localized forms of ApoAI-associated amyloidoses provided evidence of the presence of ApoAI-derived N-terminal fragments in aortic amyloid deposits [19]. In the knee joint menisci of patients with knee osteoarthritis, amyloid deposits were found to be mainly constituted by ApoAI produced in situ by chondrocytes [20].…”