Amyloid Fibrils

Proteins fold into energetically-favorable structures, with their hydrophobic amino acids on the inside and their charged and polar amino acids on the outside. Some proteins fold easily on their own but many are guided to fold correctly by proteins called chaperones.

Sometimes proteins fold into incorrect shapes, often referred to as misfolded proteins, which are degraded by the proteasome.

Inadequate cellular oversight, such as non-functioning chaperones or proteasomes due to aging or disease, can cause proteins to stay in abnormal shapes.

Mutations can cause protein misfolding if the original protein shape becomes less favorable.

Extrinsic factors, such as physical or chemical changes in the cytoplasm, force properly-folded proteins into new structures, suitable for the new environment. 

Whatever the mechanism, misfolding can expose short, hydrophobic segments of a protein causing it to become insoluble in water. Some of these hydrophobic segments that normally fold into alpha-helices can assemble into beta-sheets.

Hundreds of beta-sheets in identical misfolded proteins form hydrogen bonds and stack to form long filaments.  Two closely-packed stacks of beta-sheets associate to fo