Amyloids were first identified in association with amyloidoses, human diseases in which proteins and peptides misfold into amyloid fibrils. Subsequent studies have identified an array of functional amyloid fibrils that perform physiological roles in humans. Given the potential for the production of toxic species in amyloid assembly reactions, it is remarkable that cells can produce these functi...

Significant amounts of glycosaminoglycans (GAGs) were found in amyloid fibril preparations. Using two-dimensional electrophoresis to fractionate GAG mixtures, we quantified and identified for the first time the GAGs of the fibrils from carpal synovium of patients with amyloid associated with chronic hemodialysis. The total GAG content was small, but the GAG distribution (high relative content o...

Treatment of Alzheimer’s disease (AD) is hampered by the fact that the disease progression cannot be tracked in vivo at this time. Understanding the properties of Aβ amyloid fibrils associated with AD is imperative to finding a way to track the progression of the disease. Recently, fluorescent markers, derived from thioflavin T have been developed as markers of AD. This project examines the int...

Amyloid fibrils are a class of insoluble protein nanofibers that are formed via the self-assembly of a wide range of peptides and proteins. They are increasingly exploited for a broad range of applications in bionanotechnology, such as biosensing and drug delivery, as nanowires, hydrogels, and thin films. Amyloid fibrils have been prepared from many proteins, but there has been no definitive ch...

Amyloidosis is one of the major causes of nephrotic syndrome in adults, mainly in older patients. It is caused by the accumulation of amyloid fibrils in the extracellular tissue and while there are several types of amyloid fibrils, serum amyloid A protein has been associated with chronic inflammatory diseases. The AA type of amyloidosis usually presents with proteinuria followed by renal failure.

Serum amyloid P (SAP) is a common component of human amyloid deposits and has been identified in atherosclerotic lesions. We investigated the extent of the colocalization of SAP with apolipoprotein A-I (apoA-I), apoB, apoC-II, and apoE in human coronary arteries and explored potential roles for SAP in these regions, specifically the effect of SAP on the rate of formation and macrophage recognit...

Self-assembly of proteins into amyloid fibrils plays a key role in a multitude of human disorders that range from Alzheimer's disease to type II diabetes. Compact oligomeric species, observed early during amyloid formation, are reported as the molecular entities responsible for the toxic effects of amyloid self-assembly. However, the relation between early-stage oligomeric aggregates and late-s...

Studies by solid-state nuclear magnetic resonance (NMR) of amyloid fibrils prepared in vitro from synthetic 40-residue beta-amyloid (Abeta(1-40)) peptides have shown that the molecular structure of Abeta(1-40) fibrils is not uniquely determined by amino acid sequence. Instead, the fibril structure depends on the precise details of growth conditions. The molecular structures of beta-amyloid fibr...

The pathological signature of Alzheimer’s disease is the deposition of β-amyloid protein (Aβ). Its cleavage products, such as Aβ40 and Aβ42, form amyloid fibrils and plaques in the brains of affected individuals. Compounds that have affinity for Aβ have the ability to prevent neurotoxicity by inhibiting aggregation of amyloid fibrils. In addition, these molecules can also serve to quantify amyl...