**Abstract**

All amyloid comprises fibrillar polymers of tightly associated protein monomers. Central to the fibril structure is a highly ordered β-pleated sheet domain although this interacting region may only be a relatively short stretch of each constituent polypeptide chain. Fibril formation begins as a nucleation event based either on the constituent monomer protein or its proteolytic fragment(s). The resulting fibrils are generally chemically inert and very stable.

**Keywords:** amyloid, fibril, β-sheet, polymer, nucleation

## **1. Introduction**

The term "amyloid" is intrinsically a misnomer. It was derived in the nineteenth century to describe what was then thought to be amorphous material composed of carbohydrate (*Gk* "amyl," starch) in both plants and pathologic specimens from humans and animals. In human pathology these deposits were identified in the kidney, liver, heart, brain, and elsewhere and were often associated with organ dysfunction. In 1942, Hass [1] showed that the material was largely protein, not carbohydrate. An important observation in 1959 [2] used electron microscopy to show that the material was not amorphous but, rather, consisted of long fibrils. **Figure 1** shows an example of amyloid fibrils.

Subsequent studies have been directed to identifying the constituent proteins and clarifying the process(es) of fibril formation. Treatment for affected individuals depends upon addressing the underlying chemistry and biology. We will review these in turn.

#### **Figure 1.**

*Electron microscopic images of amyloid fibrils derived from synthetic sequences of Alzheimer β(1-42) polypeptides each containing different amino acid substitutions and yet forming characteristic fibrils, emphasizing the generalizability of amyloid fibril formation [3]. Copyright, 2005. National Academy of Sciences, used by permission.*
