98%
921
2 minutes
20
The soluble-to-toxic transformation of intrinsically disordered amyloidogenic proteins such as amyloid beta (Aβ), α-synuclein, mutant Huntingtin Protein (mHTT) and islet amyloid polypeptide (IAPP) among others are associated with disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Type 2 Diabetes (T2D), respectively. The dissolution of mature fibrils and toxic amyloidogenic intermediates, including oligomers, continues to be the pinnacle in the treatment of neurodegenerative disorders. Yet, methods to effectively and quantitatively report on the interconversion between amyloid monomers, oligomers and mature fibrils fall short. Here we describe a simplified method that implements the use of gel electrophoresis to address the transformation between soluble monomeric amyloid proteins and mature amyloid fibrils. The technique implements an optimized but well-known, simple, inexpensive, and quantitative assessment previously used to assess the oligomerization of amyloid monomers and subsequent amyloid fibrils. This method facilitates the screening of small molecules that disintegrate oligomers and fibrils into monomers, dimers, and trimers and/or retain amyloid proteins in their monomeric forms. Most importantly, our optimized method diminishes existing barriers associated with existing (alternative) techniques to evaluate fibril formation and intervention.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600300 | PMC |
http://dx.doi.org/10.1007/s12013-024-01293-x | DOI Listing |
J Histotechnol
September 2025
Department of Pathology, Peking University Third Hospital, Beijing, China.
Amyloidosis encompasses a spectrum of rare disorders characterized by extracellular amyloid deposition. Achieving an accurate early diagnosis of systemic amyloidosis necessitates biopsy-specific pathological evaluation. Formalin-fixed, paraffin-embedded liver biopsy specimens were examined using Congo red staining, electron microscopy, immunohistochemistry (IHC), immunofluorescence, and Congo red-assisted laser microdissection with mass spectrometry (LMD/MS).
View Article and Find Full Text PDFAlzheimers Dement
September 2025
Department of Neurology, Beijing TianTan Hospital, Capital Medical University, Beijing, China.
Cognitive impairment and dementia, including Alzheimer's disease (AD), pose a global health crisis, necessitating non-invasive biomarkers for early detection. This review highlights the retina, an accessible extension of the central nervous system (CNS), as a window to cerebral pathology through structural, functional, and molecular alterations. By synthesizing interdisciplinary evidence, we identify retinal biomarkers as promising tools for early diagnosis and risk stratification.
View Article and Find Full Text PDFAlzheimers Dement
September 2025
Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, South Korea.
Introduction: We developed and validated age-related amyloid beta (Aβ) positron emission tomography (PET) trajectories using a statistical model in cognitively unimpaired (CU) individuals.
Methods: We analyzed 849 CU Korean and 521 CU non-Hispanic White (NHW) participants after propensity score matching. Aβ PET trajectories were modeled using the generalized additive model for location, scale, and shape (GAMLSS) based on baseline data and validated with longitudinal data.
Front Aging Neurosci
August 2025
Yan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.
The intramembrane aspartic protease, γ-secretase, is a heterotetrameric protein complex composed of four integral membrane proteins: presenilin (PSEN), nicastrin (NCT), Anterior pharynx defective-1 (APH-1), and presenilin enhancer 2 (PEN-2). These components are sequentially assembled into a functional complex. γ-secretase is ubiquitously expressed in all cells and tissues and exhibits enzymatic activity akin to "molecular scissors" by cleaving various type I transmembrane proteins.
View Article and Find Full Text PDFBrain Commun
September 2025
Alzheimer's Disease Cooperative Study (ADCS), Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
Several studies implicate circadian rhythm disturbances in Alzheimer's disease. However, very little is known about how circadian rhythms are associated with Alzheimer's pathological biomarkers in older adults at early stages of the disease, and how these relationships map onto cognition. This cross-sectional study used 24-h accelerometry data to investigate the relationships between circadian rhythms, amyloid-β (Aβ), tau, and cognition in 68 older adults with objective early cognitive impairment.
View Article and Find Full Text PDF