A comparison of lysosomal enzymes expression levels in peripheral blood of mild- and severe-Alzheimer’s disease and MCI patients: implications for regenerative medicine approaches

The association of lysosomal dysfunction and neurodegeneration has been documented in several neurodegenerative diseases, including Alzheimer’s Disease (AD). Herein, we investigate the association of lysosomal enzymes with AD at different stages of progression of the disease (mild and severe) or with mild cognitive impairment (MCI). We conducted a screening of two classes of lysosomal enzymes: glycohydrolases (β-Hexosaminidase, β-Galctosidase, β-Galactosylcerebrosidase, β-Glucuronidase) and proteases (Cathepsins S, D, B, L) in peripheral blood samples (blood plasma and PBMCs) from mild AD, severe AD, MCI and healthy control subjects. We confirmed the lysosomal dysfunction in severe AD patients and added new findings enhancing the association of abnormal levels of specific lysosomal enzymes with the mild AD or severe AD, and highlighting the difference of AD from MCI. Herein, we showed for the first time the specific alteration of β-Galctosidase (Gal), β-Galactosylcerebrosidase (GALC) in MCI patients. It is notable that in above peripheral biological samples the lysosomes are more sensitive to AD cellular metabolic alteration when compared to levels of Aβ-peptide or Tau proteins, similar in both AD groups analyzed. Collectively, our findings support the role of lysosomal enzymes as potential peripheral molecules that vary with the progression of AD, and make them useful for monitoring regenerative medicine approaches for AD

Precision Measurement of the Boron to Carbon Flux Ratio in Cosmic Rays from 1.9 GV to 2.6 TV with the Alpha Magnetic Spectrometer on the International Space Station

Knowledge of the rigidity dependence of the boron to carbon flux ratio (B/C) is important in understanding the propagation of cosmic rays. The precise measurement of the B/C ratio from 1.9 GV to 2.6 TV, based on 2.3 million boron and 8.3 million carbon nuclei collected by AMS during the first 5 years of operation, is presented. The detailed variation with rigidity of the B/C spectral index is reported for the first time. The B/C ratio does not show any significant structures in contrast to many cosmic ray models that require such structures at high rigidities. Remarkably, above 65 GV, the B/C ratio is well described by a single power law R[superscript Δ] with index Δ=-0.333±0.014(fit)±0.005(syst), in good agreement with the Kolmogorov theory of turbulence which predicts Δ=-1/3 asymptotically.National Science Foundation (U.S.) (Grants 1455202 and 1551980)Wyle Research (Firm) (Grant 2014/T72497)United States. National Aeronautics and Space Administration (NASA Earth and Space Science Fellowship Grant HELIO15F-0005

Antiproton Flux, Antiproton-to-Proton Flux Ratio, and Properties of Elementary Particle Fluxes in Primary Cosmic Rays Measured with the Alpha Magnetic Spectrometer on the International Space Station

International audienceA precision measurement by AMS of the antiproton flux and the antiproton-to-proton flux ratio inprimary cosmic rays in the absolute rigidity range from 1 to 450 GV is presented based on 3.49 × 105antiproton events and 2.42 × 109 proton events. The fluxes and flux ratios of charged elementary particlesin cosmic rays are also presented. In the absolute rigidity range ∼60 to ∼500 GV, the antiproton ¯p, protonp, and positron eþ fluxes are found to have nearly identical rigidity dependence and the electron e− fluxexhibits a different rigidity dependence. Below 60 GV, the ( ¯ p=p), ( ¯ p=eþ), and (p=eþ) flux ratios eachreaches a maximum. From ∼60 to ∼500 GV, the ( ¯ p=p), ( ¯ p=eþ), and (p=eþ) flux ratios show no rigiditydependence. These are new observations of the properties of elementary particles in the cosmos

Observation of New Properties of Secondary Cosmic Rays Lithium, Beryllium, and Boron by the Alpha Magnetic Spectrometer on the International Space Station

We report on the observation of new properties of secondary cosmic rays Li, Be, and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV with a total of 5.4 × 106 nuclei collected by AMS during the first five years of operation aboard the International Space Station. The Li and B fluxes have an identical rigidity dependence above 7 GVand all three fluxes have an identical rigidity dependence above 30 GV with the Li=Be flux ratio of 2.0 $\pm$ 0.1. The three fluxes deviate from a single power law above 200 GV in an identical way. This behavior of secondary cosmic rays has also been observed in the AMS measurement of primary cosmic rays He, C, and O but the rigidity dependences of primary cosmic rays and of secondary cosmic rays are distinctly different. In particular, above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays

Precision Measurement of the (e++e−) Flux in Primary Cosmic Rays from 0.5 GeV to 1 TeV with the Alpha Magnetic Spectrometer on the International Space Station

We present a measurement of the cosmic ray (e++e-) flux in the range 0.5 GeV to 1 TeV based on the analysis of 10.6 million (e++e-) events collected by AMS. The statistics and the resolution of AMS provide a precision measurement of the flux. The flux is smooth and reveals new and distinct information. Above 30.2 GeV, the flux can be described by a single power law with a spectral index &gamma;=-3.170&plusmn;0.008(stat+syst)&plusmn;0.008(energyscale).</p

Precision Measurement of the Boron to Carbon Flux Ratio in Cosmic Rays from 1.9 GV to 2.6 TV with the Alpha Magnetic Spectrometer on the International Space Station

Knowledge of the rigidity dependence of the boron to carbon flux ratio (B/C) is important in understanding the propagation of cosmic rays. The precise measurement of the B/C ratio from 1.9 GV to 2.6 TV, based on 2.3 million boron and 8.3 million carbon nuclei collected by AMS during the first 5 years of operation, is presented. The detailed variation with rigidity of the B/C spectral index is reported for the first time. The B/C ratio does not show any significant structures in contrast to many cosmic ray models that require such structures at high rigidities. Remarkably, above 65 GV, the B/C ratio is well described by a single power law RΔ with index Δ = −0.333 +/- 0.014(fit) +/- 0.005(syst), in good agreement with the Kolmogorov theory of turbulence which predicts Δ = −1/3 asymptotically.</p

Towards Understanding the Origin of Cosmic-Ray Positrons

Precision measurements of cosmic ray positrons are presented up to 1 TeV based on 1.9 million positrons collected by the Alpha Magnetic Spectrometer on the International Space Station. The positron flux exhibits complex energy dependence. Its distinctive properties are (a) a significant excess starting from 25.2 +/- 1.8 GeV compared to the lower-energy, power-law trend, (b) a sharp dropoff above 284(-64)(+91) GeV, (c) in the entire energy range the positron flux is well described by the sum of a term associated with the positrons produced in the collision of cosmic rays, which dominates at low energies, and a new source term of positrons, which dominates at high energies, and (d) a finite energy cutoff of the source term of E-s = 810(-180)(+310) GeV is established with a significance of more than 4 sigma. These experimental data on cosmic ray positrons show that, at high energies, they predominantly originate either from dark matter annihilation or from other astrophysical sources

Precision Measurement of Cosmic-Ray Nitrogen and its Primary and Secondary Components with the Alpha Magnetic Spectrometer on the International Space Station

A precision measurement of the nitrogen flux with rigidity (momentum per unit charge) from 2.2 GV to 3.3 TV based on 2.2 x 10(6) events is presented. The detailed rigidity dependence of the nitrogen flux spectral index is presented for the first time. The spectral index rapidly hardens at high rigidities and becomes identical to the spectral indices of primary He, C, and O cosmic rays above similar to 700 GV. We observed that the nitrogen flux Phi(N) can be presented as the sum of its primary component Phi(P)(N) and secondary component Phi(S)(N), Phi(N) = Phi(P)(N) + Phi(S)(N), and we found Phi(N) is well described by the weighted sum of the oxygen flux Phi(O) (primary cosmic rays) and the boron flux Phi(B) (secondary cosmic rays), with Phi(P)(N) = (0.090 +/- 0.002) x Phi(O) and Phi(S)(N) = (0.62 +/- 0.02) x Phi(B) over the entire rigidity range. This corresponds to a change of the contribution of the secondary cosmic ray component in the nitrogen flux from 70% at a few GV to < 30% above 1 TV

Towards Understanding the Origin of Cosmic-Ray Electrons

Precision results on cosmic-ray electrons are presented in the energy range from 0.5 GeV to 1.4 TeV based on 28.1 x 10(6) electrons collected by the Alpha Magnetic Spectrometer on the International Space Station. In the entire energy range the electron and positron spectra have distinctly different magnitudes and energy dependences. The electron flux exhibits a significant excess starting from 42.1(-5.2)(+5.4) GeV compared to the lower energy trends, but the nature of this excess is different from the positron flux excess above 25.2 +/- 1.8 GeV. Contrary to the positron flux, which has an exponential energy cutoff of 810(-180)(+310) GeV, at the 5 sigma level the electron flux does not have an energy cutoff below 1.9 TeV. In the entire energy range the electron flux is well described by the sum of two power law components. The different behavior of the cosmic-ray electrons and positrons measured by the Alpha Magnetic Spectrometer is clear evidence that most high energy electrons originate from different sources than high energy positrons