Deciphering the Morphological Difference of Amyloid-β Fibrils in Familial and Sporadic Alzheimer's Diseases.

The aggregation of amyloid-β (Aβ) into amyloid fibrils is the major pathological hallmark of Alzheimer's disease (AD). Aβ fibrils can adopt a variety of morphologies, the relative populations of which are recently found to be associated with different AD subtypes such as familial and sporadic AD (fAD and sAD, respectively). The two AD subtypes differ in their ages of onset, AD-related genetic predispositions, and dominant Aβ fibril morphologies.

APOE regulates the transport of GM1.

Apolipoprotein E (APOE) is responsible for lipid transport, including cholesterol transport and clearance. While the ε4 allele of APOE (APOE4) is associated with a significant genetic risk factor for late-onset Alzheimer's disease (AD), no mechanistic understanding of its contribution to AD etiology has been established yet. In addition to cholesterol, monosialotetrahexosylganglioside (GM1) is a crucial lipid component in cell membranes and has been implicated in promoting the aggregation of amyloid beta protein (Aβ), a key protein associated with AD.

Direct Observation of Seeded Conformational Conversion of hIAPP Reveals the Mechanisms for Morphological Dependence and Asymmetry of Fibril Growth.

Rapid growth of amyloid fibrils a seeded conformational conversion of monomers is a critical step of fibrillization and important for disease transmission and progression. Amyloid fibrils often display diverse morphologies with distinct populations, and yet the molecular mechanisms of fibril elongation and their corresponding morphological dependence remain poorly understood. Here, we computationally investigated the single-molecular growth of two experimentally resolved human islet amyloid polypeptide fibrils of different morphologies.

Amyloid Aggregation and Liquid-Liquid Phase Separation from the Perspective of Phase Transitions.

Amyloid aggregation describes the aberrant self-assembly of peptides into ordered fibrils characterized by cross-β spine cores and is associated with many neurodegenerative diseases and Type 2 diabetes. Oligomers, populated during the early stage of aggregation, are found to be more cytotoxic than mature fibrils. Recently, many amyloidogenic peptides have been reported to undergo liquid-liquid phase separation (LLPS)─a biological process important for the compartmentalization of biomolecules in living cells─prior to fibril formation.

Enhanced Label-Free Nanoplasmonic Cytokine Detection in SARS-CoV-2 Induced Inflammation Using Rationally Designed Peptide Aptamer.

Rapid and precise serum cytokine quantification provides immense clinical significance in monitoring the immune status of patients in rapidly evolving infectious/inflammatory disorders, examplified by the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, real-time information on predictive cytokine biomarkers to guide targetable immune pathways in pathogenic inflammation is critically lacking, because of the insufficient detection range and detection limit in current label-free cytokine immunoassays. In this work, we report a highly sensitive localized surface plasmon resonance imaging (LSPRi) immunoassay for label-free Interleukin 6 (IL-6) detection utilizing rationally designed peptide aptamers as the capture interface.