Research Projects

Proteins

Aβ - Introduction

Alzheimer’s disease (AD) is a degenerative brain condition that results in dementia. It usually starts in late-middle or old age and is often characterized by progressive memory loss, impaired thinking, disorientation and changes in personality and mood. The disease is marked by the degeneration of brain neurons and the presence of neurofibrillary tangles and amyloid plaques. Both the tangles and plaques observed in the brains of AD patients are caused by protein aggregation. The tangles are composed of a protein called tau. In healthy neurons, this protein provides stabilization for the microtubule support structure within the cell. In AD, tau is hyperphosphorylated, causing it to aggregate and form insoluble tangles within the cell, resulting in cell death. The plaques are amyloid fibrils composed predominantly of a protein called amyloid beta (Aβ). Aβ is formed from a larger protein called amyloid precursor protein (APP) by enzymatic cleavage to produce peptides that have 40 or 42 amino acids. These peptides, Aβ40 and Aβ42, are normally cleared out of the brain in healthy individuals but in those afflicted with AD, the peptides, particularly Aβ42, accumulate extracellularly and form plaques.

While our investigation of the Aβ peptides has been in progress for a number of years in collaboration with Teplow and other experts [1], we have recently begun to include the protein tau in our studies, too. The major goals of our Aβ and tau research are to

using mass spectrometry/ion mobility methods in combination with molecular mechanics simulations.

For the Aβ peptides we attempt to reach these goals by studying the following topics which are addressed in some detail on the following web pages.