Amyloid contained in the knee joint meniscus is formed from apolipoprotein A-I

To determine the chemical nature of amyloid deposits found in knee joint menisci.

Amyloid was extracted from the menisci of 3 adults who underwent knee joint replacement surgery. The primary structural features of the purified proteins were determined by sequential Edman degradation and tandem mass spectrometry (MS/MS). Tissue specimens were also subjected to in situ hybridization analysis, as well as complementary DNA cloning by reverse transcriptase-polymerase chain reaction (RT-PCR). Additionally, specimens from these 3 patients, as well as other patients with amyloid in the knee joint menisci, were examined immunohistochemically.

Amino acid sequence and MS/MS analyses of the extracts revealed the presence of 60-77-residue components identical to the N-terminal portion of apolipoprotein A-I (Apo A-I). The Apo A-I nature of the amyloid was confirmed by the demonstration that the green birefringent congophilic deposits in the 7 meniscus samples were recognized by an anti-human Apo A-I antibody. That the meniscus itself was the source of the amyloidogenic protein was evidenced through Southern blot analysis, in which an Apo A-I product was generated by RT-PCR from synovial tissue, and further, by the demonstration that the cytoplasm of chondrocytes reacted with the specific Apo A-I probe used for in situ hybridization and was immunostained by the anti-Apo A-I antiserum.

Amyloid in the knee joint menisci is formed from Apo A-I that is produced by chondrocytes within the meniscal cartilage. This entity represents yet another localized form of amyloidosis associated with the aging process and may be of pathophysiologic import.