Misfolding and aggregation of normally soluble proteins into amyloid fibrils and their deposition and accumulation underlies a variety of clinically significant diseases. Fibrillar aggregates with amyloid-like properties can also be generated in vitro from pure proteins and peptides, including those not known to be associated with amyloidosis. Whereas biophysical studies of amyloid-like fibrils...

A central issue in the pathogenesis of Alzheimer's disease (AD) is the relationship between amyloid deposition and neurofibrillary tangle formation. To determine whether amyloid fibril formation affects the phosphorylation state of tau, primary cultures of fetal rat hippocampal and human cortical neurons were treated with beta-amyloid (beta A) in a soluble, amorphous-aggregated, or fibrillar fo...

Abstract Introduction Recent studies have found that mid-life sleep disruption is associated with the development of Alzheimer’s disease-related neuropathology, including deposition amyloid beta. Yet, mechanism connecting disruption, particularly over chronic timescales, and downstream pathology remains unclear. Methods In this study, we evaluated impact has on neuroinflammation beta plaques in...

BACKGROUND AND PURPOSE In the elderly, cerebral ischemia (CI) occurs in the presence of high levels of amyloid. Neuroinflammation plays a critical role in the pathophysiology of Alzheimer's disease and CI. This study examined infarct size, neuroinflammation, and cognitive deficits over time in rat models of Alzheimer's disease and CI. METHODS beta-amyloid toxicity was modeled using bilateral ...

In a multimodal PET imaging approach, we determined the differential contribution of neurofibrillary tangles (measured with [18F]AV-1451) and beta-amyloid burden (measured with [11C]PiB) on degree of neurodegeneration (i.e., glucose metabolism measured with [18F]FDG-PET) in patients with Alzheimer's disease. Across brain regions, we observed an interactive effect of beta-amyloid burden and tau ...

Islet amyloid occurs in >90% of type 2 diabetic patients and may play a role in the pathogenesis of this disease. To determine whether islet amyloid occurs diffusely throughout the pancreas, whether it affects islets equally, and whether it decreases islet endocrine cells, we characterized islet amyloidosis by computerized fluorescence microscopy in transgenic mice that develop typical islet am...

Mempasin 2, a beta-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of beta-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been esta...