Apolipoprotein D (apoD) is expressed in the brain and levels are increased in affected brain regions in Alzheimer's disease (AD). The role that apoD may play in regulating AD pathology has not been addressed. Here, we crossed both apoD-null mice and Thy-1 human apoD transgenic mice with APP-PS1 amyloidogenic AD mice. Loss of apoD resulted in a nearly 2-fold increase in hippocampal amyloid plaqu...

The 16–22 amino acid fragment of the β-amyloid peptide associated with the Alzheimer’s disease, Aβ, is capable of forming amyloid fibrils. Here we study the aggregation mechanism of Aβ16−22 peptides by unbiased thermodynamic simulations at the atomic level for systems of one, three and six Aβ16−22 peptides. We find that the isolated Aβ16−22 peptide is mainly a random coil in the sense that both...

As is the case in numerous natural processes, enzymatic phosphorylation can be used in the laboratory to influence the conformational populations of proteins. In nature, this information is used for signal transduction or energy transfer, but has also been shown to play an important role in many diseases like tauopathies or diabetes. With the goal of determining the effect of phosphorylation on...

The 16–22 amino acid fragment of the β-amyloid peptide associated with the Alzheimer’s disease, Aβ, is capable of forming amyloid fibrils. Here we study the aggregation mechanism of Aβ16−22 peptides by unbiased thermodynamic simulations at the atomic level for systems of one, three and six Aβ16−22 peptides. We find that the isolated Aβ16−22 peptide is mainly a random coil in the sense that both...

Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109-122, recapitulates many properties of the full...

The understanding of the key mechanisms behind human brain deterioration in Alzheimer' disease (AD) is a highly active field of research. The most widespread hypothesis considers a cascade of events initiated by amyloid-β peptide fibrils that ultimately lead to the formation of the lethal amyloid plaques. Recent studies have shown that other agents, in particular magnetite, can also play a pivo...

Inactivity, obesity, and insulin resistance are significant risk factors for the development of Alzheimer's disease (AD). Several studies have demonstrated that diet-induced obesity, inactivity, and insulin resistance exacerbate the neuropathological hallmarks of AD. The aggregation of β-amyloid peptides is one of these hallmarks. β-Site amyloid precursor protein-cleaving enzyme 1 (BACE1) is th...

Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ permeabilize cellular membranes, presumably through a pore formation mechanism. Owing to their structural and stoichiometric heterogeneity, the structure these pores remains be characterized. We studied functional Aβ42-pore equivalent, created by fusing Aβ42 olig...