γS-crystallin is a major structural component of the human eye lens, which maintains its stability over the lifetime of an organism with negligible turnover. The G57W mutant of human γS-crystallin (abbreviated hereafter as γS-G57W) is associated with dominant congenital cataracts. In order to provide a structural basis for the ability of γS-G57W causing cataract, we have cloned, overexpressed, isolated and purified the protein. The 2D [N-H]-HSQC spectrum recorded with uniformly C/N-labelled γS-G57W was highly dispersed indicating the protein to adopt an ordered conformation. In this paper, we report almost complete sequence-specific H, C and N resonance assignments of γS-G57W using a suite of heteronuclear 3D NMR experiments.
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http://dx.doi.org/10.1007/s12104-017-9779-y | DOI Listing |
Background: New innovations take a long time to be utilized into routine healthcare due to intrinsic and practical barriers. Implementation science can identify such barriers and offer potential solutions to speed up this process. Blood-based biomarkers (BBBMs) may enable scalable confirmation of amyloid pathology in the Alzheimer's disease (AD) care pathway with test performance similar to cerebrospinal fluid (CSF) testing and positron emission tomography (PET), so-called confirmatory biomarkers as they can corroborate amyloid pathology with high certainty.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Background: Diagnosing sporadic early-onset AD (EOAD, age-at-onset<65) is challenging: in the multi-center Longitudinal Early-onset Alzheimer's Disease Study, ∼25% of patients with clinically diagnosed EOAD are amyloid-PET-negative. Here we used FDG-PET to characterize the heterogeneity of hypometabolic profiles in these patients and better identify underlying etiologies.
Method: Seventy-four amyloid-PET-negative patients with clinical diagnosis of sporadic EOAD (MCI or mild dementia stage) underwent FDG-PET.
Background: Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages.
Method: From the AMYPAD-PNHS cohort, we included a total of 1323 non-demented individuals, including 1094 amyloid-negative, and 229 amyloid-positive participants (Table 1).
Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neurodegenerative disease that is often comorbid with Alzheimer's disease (AD) and for which there are no reliable specific chemical or PET biomarkers available. Recent progress in disease-modifying treatments for AD elevates the need for reliable in vivo detection of LATE and other comorbid neurodegenerative diseases. The promise of postmortem and antemortem MRI studies in LATE is that they will lead to the discovery of patterns of neurodegeneration associated with TDP-43 pathology that could be reliably detected in vivo and used as a biomarker of LATE.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Background: With the development of disease modifying therapies targeting specific pathologies, accurate in vivo biomarkers have become increasingly important for disease classification. Recently, tests for neuronal α-synuclein (Lewy body) pathology have become available, complementing pre-existing tests for Alzheimer's disease (AD) pathology (Aβ and tau fluid and PET biomarkers) and vascular disease (MRI). Here, we aimed to identify and characterize data-driven pathology-based subtypes using these biomarkers.
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