Dataset Information

Amyloid-? Plaques in Clinical Alzheimer's Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder with clinical manifestations of progressive memory decline and loss of executive function and language. AD affects an estimated 5.3 million Americans alone and is the most common form of age-related dementia with a rapidly growing prevalence among the aging population-those 65?years of age or older. AD is characterized by accumulation of aggregated amyloid-beta (A?) in the brain, which leads to one of the pathological hallmarks of AD-A? plaques. As a result, A? plaques have been extensively studied after being first described over a century ago. Advances in brain imaging and quantitative measures of A? in biological fluids have yielded insight into the time course of plaque development decades before and after AD symptom onset. However, despite the fundamental role of A? plaques in AD, in vivo measures of individual plaque growth, growth distribution, and dynamics are still lacking. To address this question, we combined stable isotope labeling kinetics (SILK) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging in an approach termed SILK-SIMS to resolve plaque dynamics in three human AD brains. In human AD brain, plaques exhibit incorporation of a stable isotope tracer. Tracer enrichment was highly variable between plaques and the spatial distribution asymmetric with both quiescent and active nanometer sub-regions of tracer incorporation. These data reveal that A? plaques are dynamic structures with deposition rates over days indicating a highly active process. Here, we report the first, direct quantitative measures of in vivo deposition into plaques in human AD brain. Our SILK-SIMS studies will provide invaluable information on plaque dynamics in the normal and diseased brain and offer many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development.

SUBMITTER: Wildburger NC

PROVIDER: S-EPMC5874304 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Amyloid-β Plaques in Clinical Alzheimer's Disease Brain Incorporate Stable Isotope Tracer <i>In Vivo</i> and Exhibit Nanoscale Heterogeneity.

Wildburger Norelle C NC Gyngard Frank F Guillermier Christelle C Patterson Bruce W BW Elbert Donald D Mawuenyega Kwasi G KG Schneider Theresa T Green Karen K Roth Robyn R Schmidt Robert E RE Cairns Nigel J NJ Benzinger Tammie L S TLS Steinhauser Matthew L ML Bateman Randall J RJ

Frontiers in neurology 20180322

Alzheimer's disease (AD) is a neurodegenerative disorder with clinical manifestations of progressive memory decline and loss of executive function and language. AD affects an estimated 5.3 million Americans alone and is the most common form of age-related dementia with a rapidly growing prevalence among the aging population-those 65 years of age or older. AD is characterized by accumulation of aggregated amyloid-beta (Aβ) in the brain, which leads to one of the pathological hallmarks of AD-Aβ pl ...[more]

PMID: 29623063

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Project description:BackgroundKnowledge of the physiologic requirement for iron, the core index for the formulation of a dietary reference intake (DRI), is of great importance for the health of a pregnant woman and her fetus, and can help a mother accurately plan her iron supplementation. However, direct measurements of the physiologic requirement for iron during pregnancy are still lacking.MethodEleven women of reproductive age from Hebei Province, China, who planned to become pregnant in the near future, were enrolled between January and March 2015 and included in the final analysis. Subjects participated in a 2-week metabolic trial in which they consumed 50 mg of the stable isotope 58Fe, and were then followed for ~ 2 years. The abundance of 58Fe and the total iron concentration in the circulation were measured using Multi-collector Inductively-Coupled Plasma Mass Spectrometry and Atomic Absorption Spectroscopy, respectively. The physiologic requirement for iron during pregnancy was then calculated by the formula derived from our previously published work.ResultsThe mean physiologic requirement for iron in the 11 subjects, across their entire pregnancies, was 3.05 mg.d- 1 in total and 44.0 μg.kg- 1.d- 1 after adjustment for body mass. The physiologic requirements for iron in the first, second, and third trimesters were 2.04 mg.d- 1, 3.26 mg.d- 1, and 4.13 mg.d- 1, respectively. When adjusted for body mass, the physiologic requirements for iron in different trimesters were 32.3 μg.kg- 1.d- 1, 46.9 μg.kg- 1.d- 1, and 55.7 μg.kg- 1.d- 1, respectively.ConclusionWe preliminarily explored the physiologic requirement for iron in pregnant women. The data demonstrated that pregnant women needed about twice iron than non-pregnant women. This research may be helpful for the design of future studies and the modification of iron DRIs.Trial registrationChiCTR, ChiCTR-OCH-14004302. Registered 14 February 2014, http://www.chictr.org.cn/showproj.aspx?proj=5267.

Dataset Information

Amyloid-? Plaques in Clinical Alzheimer's Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity.

Publications

Amyloid-β Plaques in Clinical Alzheimer's Disease Brain Incorporate Stable Isotope Tracer <i>In Vivo</i> and Exhibit Nanoscale Heterogeneity.

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