scholarly journals Distribution of isomerized and racemized amyloid β isoforms in sporadic Alzheimer’s disease using ion‐mobility mass spectrometry

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Soumya Mukherjee ◽  
Keyla Perez ◽  
Larissa Cristina Lago ◽  
Stephan Klatt ◽  
Ian Birchall ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ion Mobility ◽  
Amyloid Β ◽  
Ion Mobility Mass Spectrometry ◽  
Sporadic Alzheimer’S Disease

Sialylation Fine-Tunes Glycoprotein Structural Microheterogeneity Associated with Alzheimer’s Disease as Captured by Native Ion Mobility-Mass Spectrometry

2020 ◽  
Author(s):  
Gongyu Li ◽  
Ashley Phetsanthad ◽  
Min Ma ◽  
Qinying Yu ◽  
Ashita Nair ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ion Mobility ◽  
Sialic Acids ◽  
Fine Tuning ◽  
Ion Mobility Mass Spectrometry ◽  
Structure Sensitive ◽  
Terminal Structure

Protein sialylation has been closely linked to many diseases including Alzheimer’s disease (AD) and is broadly implicated in therapeutics in a terminal structure-sensitive manner. However, how sialylation structurally affects mature glycoproteins and how such effect is linked biochemically to AD progression largely remain ill-defined and are, likely beset with the lack of appropriate strategies capable of rapid and in situ manipulation of sialic acids on mature glycoproteins. Herein, we report the use of native ion mobility-mass spectrometry (IM-MS)-based structural probing methodology, enabling well-controlled, synergistic and in situ manipulation of mature glycoproteins and attached sialic acids. Cell viability experiments and IM-MS suggest that the dysregulating effects of transferrin sialylation on the iron-enhanced Aβ cytotoxicity acts through sialylation-dependent Aβ and iron co-importing pathway. Meanwhile, native gel electrophoresis and IM-MS reveal the sialylation-regulated transferrin dimerization tendency. Collectively, IM-MS is adapted to capture key sialylation intermediates involved in fine-tuning AD-associated glycoprotein structural micoheterogeneity. Our results may shed new lights on AD-modifying strategies based on sialylation-regulated glycoprotein functions and cytotoxicity.

Sialylation Fine-Tunes Glycoprotein Structural Microheterogeneity Associated with Alzheimer’s Disease as Captured by Native Ion Mobility-Mass Spectrometry

2020 ◽  
Author(s):  
Gongyu Li ◽  
Ashley Phetsanthad ◽  
Min Ma ◽  
Qinying Yu ◽  
Ashita Nair ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ion Mobility ◽  
Sialic Acids ◽  
Fine Tuning ◽  
Ion Mobility Mass Spectrometry ◽  
Structure Sensitive ◽  
Terminal Structure

Protein sialylation has been closely linked to many diseases including Alzheimer’s disease (AD) and is broadly implicated in therapeutics in a terminal structure-sensitive manner. However, how sialylation structurally affects mature glycoproteins and how such effect is linked biochemically to AD progression largely remain ill-defined and are, likely beset with the lack of appropriate strategies capable of rapid and in situ manipulation of sialic acids on mature glycoproteins. Herein, we report the use of native ion mobility-mass spectrometry (IM-MS)-based structural probing methodology, enabling well-controlled, synergistic and in situ manipulation of mature glycoproteins and attached sialic acids. Cell viability experiments and IM-MS suggest that the dysregulating effects of transferrin sialylation on the iron-enhanced Aβ cytotoxicity acts through sialylation-dependent Aβ and iron co-importing pathway. Meanwhile, native gel electrophoresis and IM-MS reveal the sialylation-regulated transferrin dimerization tendency. Collectively, IM-MS is adapted to capture key sialylation intermediates involved in fine-tuning AD-associated glycoprotein structural micoheterogeneity. Our results may shed new lights on AD-modifying strategies based on sialylation-regulated glycoprotein functions and cytotoxicity.

scholarly journals Wie kleine Amyloid-β-Peptide zum großen Problem im Gehirn werden können

BIOspektrum ◽  
2021 ◽  
Vol 27 (7) ◽  
pp. 705-708
Author(s):  
René Zangl ◽  
Nina Morgner
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Properties ◽  
Ion Mobility Spectrometry ◽  
Ion Mobility ◽  
Amyloid Β ◽  
Amyloid Β Peptide

AbstractThe formation of amyloid-β oligomers plays a key role in the onset of Alzheimer’s disease. We investigated the aggregation of amyloid-β oligomers by mass spectrometry and ion mobility spectrometry, revealing those structural properties, which lead to the formation of mature fibrils. We can show that the arrangement of the first oligomers is crucial for the topology of the resulting species, leading to the formation of non-toxic aggregates or fibrils.

scholarly journals PLASMA BIOMARKER FOR ALZHEIMER’S DISEASE: ARE WE READY NOW FOR CLINICAL PRACTICE AND DRUG TRIALS?

2018 ◽  
pp. 1-2
Author(s):  
A. Nakamura
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Utility ◽  
Large Scale ◽  
Amyloid Β ◽  
Imaging Biomarker ◽  
Validation Dataset ◽  
Data Sets ◽  
Detailed Kinetics

To facilitate disease-modifying clinical trials for Alzheimer’s Disease (AD), a blood-based amyloid-β (Aβ) biomarker, which can accurately detect an early pathological signature of AD at prodromal or preclinical stages, has been strongly desired, because it is simpler, less invasive and less costly compared to PET or lumbar puncture. Despite plasma Aβ biomarkers having been extensively investigated, most studies failed to demonstrate clinical utility (1, 2), and at the end of 2016, there was a rather pessimistic mood that this objective might be impossible to realize (3). However, since the latter half of 2017, the situation appears to have changed dramatically, in that several groups have reported potential clinical utility of plasma Aβ biomarkers using different methodologies (4-7). Especially, immunoprecipitation followed by mass spectrometry (IP-MS) assays have shown promising converging evidence. In 2014, we, the National Center for Geriatrics and Gerontology (NCGG) and Koichi Tanaka Mass Spectrometry Research Laboratory at Shimadzu Corporation (Shimadzu), reported that the plasma ratio of Aβ1-42 to a novel APP669-711 fragment (APP669–711/Aβ 1–42) as determined by IP-MS could discriminate high Aβ (Aβ+) individuals from low Aβ (Aβ-) individuals (classified using PiB-PET) with more than 90% accuracy (n=62) (8). In 2017, the Washington University group analyzed detailed kinetics of plasma Aβs, and reported that Aβ42/Aβ40 as measured by IP-MS could distinguish Aβ+ and Aβ- individuals with 88.7% areas under the curve value (n=41) (5). Then very recently, we, in collaboration with the Australian Imaging, Biomarker and Lifestyle Study of Aging (AIBL), have demonstrated that plasma biomarkers, APP669-711/Aβ1-42, Aβ1-40/Aβ1-42, and their composites (composite biomarker), as generated by improved IP-MS methodology performs very well in larger independent datasets: a discovery dataset (NCGG, n=121) and a validation dataset (AIBL, n=252 which includes n=111 PiB-PET and 141 with other ligands) both of which included individuals with normal cognition, MCI and AD. Particularly, the composite biomarker showed very high AUCs in both datasets (discovery 96.7%, n=121, and validation 94.1%, n=111) with accuracy c.a. 90% when using PiB-PET as standard of truth. The findings of the study were considered to be robust, reproducible and reliable because biomarker performance was validated in a blinded manner using independent data sets (Japan and Australia) and involved an established large-scale multicenter cohort (AIBL).

Amyloid β protein in plasma from patients with sporadic Alzheimer's disease

1996 ◽  
Vol 141 (1-2) ◽  
pp. 65-68 ◽  
Author(s):  
Akira Tamaoka ◽  
Tetsuo Fukushima ◽  
Naoya Sawamura ◽  
Kin'ya Ishikawa ◽  
Eiichi Oguni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Sporadic Alzheimer’S Disease ◽  
Β Protein

Melatonin Attenuates Memory Impairment, Amyloid-β Accumulation, and Neurodegeneration in a Rat Model of Sporadic Alzheimer’s Disease

2015 ◽  
Vol 47 (1) ◽  
pp. 103-116 ◽  
Author(s):  
Ekaterina A. Rudnitskaya ◽  
Natalia A. Muraleva ◽  
Kseniya Yi. Maksimova ◽  
Elena Kiseleva ◽  
Nataliya G. Kolosova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Memory Impairment ◽  
Amyloid Β ◽  
Sporadic Alzheimer’S Disease
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