Impact of aging on copper isotopic composition in the murine brain.

Aging is the main risk factor for Alzheimer's disease (AD). AD is linked to alterations in metal homeostasis and changes in stable metal isotopic composition can occur, possibly allowing the latter to serve as relevant biomarkers for potential AD diagnosis. Copper stable isotopes are used to investigate changes in Cu homeostasis associated with various diseases. Prior work has shown that in AD mouse models, the accumulation of 63Cu in the brain is associated with the disease's progression. However, our understanding of how the normal aging process influences the brain's isotopic composition of copper remains limited. In order to determine the utility and predictive power of Cu isotopes in AD diagnostics, we aim-in this study-to develop a baseline trajectory of Cu isotopic composition in the normally aging mouse brain. We determined the copper concentration and isotopic composition in brains of 30 healthy mice (WT) ranging in age from 6 to 12 mo, and further incorporate prior data obtained for 3-mo-old healthy mice; this range approximately equates to 20-50 yr in human equivalency. A significant 65Cu enrichment has been observed in the 12-mo-old mice compared to the youngest group, concomitant with an increase in Cu concentration with age. Meanwhile, literature data for brains of AD mice display an enrichment in 63Cu isotope compared to WT. It is acutely important that this baseline enrichment in 65Cu is fully constrained and normalized against if any coherent diagnostic observations regarding 63Cu enrichment as a biomarker for AD are to be developed.

Copper Isotope Compositions Measured Using a Sapphire Dual Path MC-ICPMS with a Collision/Reaction Cell.

We present a new approach to Cu isotopic measurements using a state-of-the-art Nu Sapphire multicollector inductively coupled plasma source mass spectrometer equipped with a collision/reaction cell (CRC-MC-ICPMS). We investigate the effects of Na doping and Cu concentration mismatch between bracketing standard and unknown samples and demonstrate the efficacy of introducing a He-H2 gas mix into the CRC to efficiently eliminate the sample matrix-based 40Ar23Na+ isobaric interference on 63Cu+. This capability is crucial when measuring samples with high Na/Cu ratios, such as some biological samples, which have significantly different chemical compositions compared to most geological samples. Moreover, considering the necessity of obtaining large data sets for biological samples to ensure reliable interpretations, the implementation of a CRC for mitigating the 40Ar23Na+ interference offers the advantage of minimizing the requirement for extensive Cu chemical separation procedure prior to Cu isotopic measurements. Our results demonstrate that the accurate determination of the δ65Cu values is achievable for samples with Na/Cu concentration ratios of up to ∼65, even when measuring 100 ppb Cu solutions (equivalent to a signal of ∼3.5-4 V total Cu). Furthermore, our results showcase a good short-term repeatability on δ65Cu for pure Cu standard solutions (NIST SRM 976 and Cu-IPGP), typically of 0.05‰ (2 SD) when measuring >50 ppb Cu solutions. Our long-term external reproducibility stands at approximately 0.07‰ (2 SD). This value accounts for the variable Cu concentrations analyzed across the different analytical sequences (from 10 to 100 ppb Cu solutions). To validate the robustness of our analytical method, we first conduct a comparison between data sets from mice brains processed twice through column chemistry using a Thermo Finnigan Neptune MC-ICPMS and a Nu Sapphire CRC-MC-ICPMS in CRC mode. This comparison serves to verify the reliability of our method for measuring Cu isotopic composition using the CRC on samples with a low Na/Cu ratio after traditional chemical processing. Then, we compare the data sets obtained for biological standards (tuna fish ERM-CE 464 (IRMM) and human serum Seronorm Trace Elements Serum L-1) processed either once, or twice, through column chemistry and demonstrate that the CRC allows accurate Cu isotopic measurements of the samples processed only once and therefore with a higher Na/Cu ratio.

Primordial formation of major silicates in a protoplanetary disc with homogeneous 26Al/27Al.

Understanding the spatial variability of initial 26Al/27Al in the solar system, i.e., (26Al/27Al)0, is of prime importance to meteorite chronology, planetary heat production, and protoplanetary disc mixing dynamics. The (26Al/27Al)0 of calcium-aluminum-rich inclusions (CAIs) in primitive meteorites (~5 × 10-5) is frequently assumed to reflect the (26Al/27Al)0 of the entire protoplanetary disc, and predicts its initial 26Mg/24Mg to be ~35 parts per million (ppm) less radiogenic than modern Earth (i.e., Δ'26Mg0 = -35 ppm). Others argue for spatially heterogeneous (26Al/27Al)0, where the source reservoirs of most primitive meteorite components have lower (26Al/27Al)0 at ~2.7 × 10-5 and Δ'26Mg0 of -16 ppm. We measured the magnesium isotope compositions of primitive meteoritic olivine, which originated outside of the CAI-forming reservoir(s), and report five grains whose Δ'26Mg0 are within uncertainty of -35 ppm. Our data thus affirm a model of a largely homogeneous protoplanetary disc with (26Al/27Al)0 of ~5 × 10-5, supporting the accuracy of the 26Al→26Mg chronometer.

Short time interval for condensation of high-temperature silicates in the solar accretion disk.

Chondritic meteorites are made of primitive components that record the first steps of formation of solids in our Solar System. Chondrules are the major component of chondrites, yet little is known about their formation mechanisms and history within the solar protoplanetary disk (SPD). We use the reconstructed concentrations of short-lived (26)Al in chondrules to constrain the timing of formation of their precursors in the SPD. High-precision bulk magnesium isotopic measurements of 14 chondrules from the Allende chondrite define a (26)Al isochron with (26)Al/(27)Al = 1.2(±0.2) × 10(-5) for this subset of Allende chondrules. This can be considered to be the minimum bulk chondrule (26)Al isochron because all chondrules analyzed so far with high precision (∼50 chondrules from CV and ordinary chondrites) have an inferred minimum bulk initial ((26)Al/(27)Al) ≥ 1.2 × 10(-5). In addition, mineral (26)Al isochrons determined on the same chondrules show that their formation (i.e., fusion of their precursors by energetic events) took place from 0 Myr to ∼2 Myr after the formation of their precursors, thus showing in some cases a clear decoupling in time between the two events. The finding of a minimum bulk chondrule (26)Al isochron is used to constrain the astrophysical settings for chondrule formation. Either the temperature of the condensation zone dropped below the condensation temperature of chondrule precursors at ∼1.5 My after the start of the Solar System or the transport of precursors from the condensation zone to potential storage sites stopped after 1.5 My, possibly due to a drop in the disk accretion rate.