Page 100 - Textbook of Pathology, 6th Edition

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SECTION I

General Pathology and Basic Techniques

Figure 4.10 Pathogenesis of two main forms of amyloid deposition (AL = Amyloid light chain; AA = Amyloid-associated protein; GAG =
glycosaminoglycan; AP = Amyloid P component). The sequence on left shows general schematic representation common to both major forms of
amyloidogenesis.

1. Pool of amyloidogenic precursor protein is present in haemodialysis) and prionosis (in which β-pleated sheet is
circulation in different clinical settings and in response to formed de novo).
stimuli e.g. increased hepatic synthesis of AA or ATTR, 5. The role of non-fibrillar components such as AP, apoE and
increased synthesis of AL etc. GAGs in amyloidosis is unclear; probably they facilitate in
2. A nidus for fibrillogenesis, meaning thereby an alteration aggregation of proteins and protein folding leading to fibril
in microenvironment, to stimulate deposition of amyloid formation, substrate adhesion and protection from
protein is formed. This alteration involves changes and degradation.
interaction between basement membrane proteins and Based on this general pathogenesis, deposition of AL and
amyloidogenic protein. AA amyloid is briefly outlined below:
3. Partial degradation or proteolysis occurs prior to deposition
of fibrillar protein which may occur in macrophages or Deposition of AL Amyloid
reticuloendothelial cells e.g. partial degradation of AL, AA. 1. The stimulus for production of AL amyloid is some
4. Exceptions to this generalisation, however, are seen in ATTR disorder of immunoglobulin synthesis e.g. multiple myeloma,
(heredofamilial type in which there are amino acid mutations B cell lymphoma, other plasma cell dyscrasias.
in most cases), Aβ2M (in which there are elevated levels of 2. Excessive immunoglobulin production is in the form of
normal β2M protein which remain unfiltered during monoclonal gammopathy i.e. there is production of either intact