Noriko Oshima

Effect of Apolipoprotein E Allele ε4 on the Initial Phase of Amyloid β-Protein Accumulation in the Human Brain

Deposition of amyloid β-protein (Aβ), a hallmark of Alzheimers disease, occurs to some extent in the brains of most elderly individuals. We sought to learn when Aβ deposition begins and how deposition is affected by apolipoprotein E allele e4, a strong risk factor for late-onset Alzheimers disease. Using an improved extraction protocol and specific enzyme-linked immunosorbent assay, we quantified the levels of Aβ40 and Aβ42 in the insoluble fractions of brains from 105 autopsy cases, aged 22 to 81 years at death, who showed no signs of dementia. Aβ40 and Aβ42 were detected in the insoluble fractions from all of the brains examined; low levels were even found in the brains of patients as young as 20 to 30 years of age. The incidence of significant Aβ accumulation increased age-dependently, with Aβ42 levels beginning to rise steeply in some patients in their late 40s, accompanied by much smaller increases in Aβ40 levels. The presence of the apolipoprotein E e4 allele was found to significantly enhance the accumulation of Aβ42 and, to a lesser extent, that of Aβ40. These findings strongly suggest that the presence of e4 allele results in an earlier onset of Aβ42 accumulation in the brain.

Aging of black carbon in outflow from anthropogenic sources using a mixing state resolved model: Model development and evaluation

Received 29 June 2008; revised 26 November 2008; accepted 5 January 2009; published 27 March 2009. [1] The mixing state of black carbon (BC) aerosols, namely, the degree to which BC particles are coated with other aerosol components, has been recognized as important for evaluating aerosol radiative forcing. In order to resolve the BC mixing state explicitly in model simulations, a two-dimensional aerosol representation, in which aerosols are given for individual particle diameters and BC mass fractions, is introduced. This representation was incorporated into an aerosol module, the Model of Aerosol Dynamics, Reaction, Ionization, and Dissolution (MADRID), and a new box model, MADRID-BC, was developed. MADRID-BC can accurately simulate changes in the entire BC mixing state resulting from condensation/evaporation processes. Aircraft observations conducted in March 2004 show that the mass fraction of thickly coated BC particles increased in air horizontally transported out from an urban area in Japan over the ocean. MADRID-BC generally reproduces this feature well when observed bulk aerosol concentrations are used as constraints. The model simulations in this particular case show that for particles with BC core diameters of 100–200 nm, the particle diameters, including both core and coating materials, had already increased by a factor of 1.6 on average when they left the source region and by as large as a factor of 1.9 of the BC core diameters after their transport over the ocean for a half day. The model simulations also show that 58% of the total condensed mass was partitioned onto BC-free particles during transport, indicating their importance for the BC mixing state. Although the model simulations are applied to a limited number of the observations in this study, they clearly show the time evolution of the coating thicknesses of BC-containing particles, which is necessary for calculating aerosol optical properties and cloud condensation nuclei activities.

Aging of black carbon in outflow from anthropogenic sources using a mixing state resolved model: 2. Aerosol optical properties and cloud condensation nuclei activities

Received 28 December 2008; revised 12 May 2009; accepted 24 June 2009; published 19 September 2009. [1] The Model of Aerosol Dynamics, Reaction, Ionization, and Dissolution with resolution of a mixing state of black carbon (BC) (referred to as MADRID-BC hereinafter) has recently been developed to accurately simulate the time evolution of the entire BC mixing state. In this study, we apply MADRID-BC to evaluate the influence of changes in BC mixing state on aerosol optical properties and cloud condensation nuclei (CCN) activities in air parcels horizontally transported out from an urban area in Japan within the planetary boundary layer (PBL) over the ocean. The evaluation shows that the coatings on BC particles enhance light absorption at a wavelength of 550 nm by 38% in air leaving the source region and by 59% after transport over the ocean for half a day. When the model treats aerosols using the conventional size-resolved sectional representation that does not resolve BC mixing states, the simulated absorption coefficients and single scattering albedos are greater by 35–44% and smaller by 7–13%, respectively, than those from a simulation that resolves the BC mixing state. These results indicate that it is essential to take into account BC-free particles in atmospheric models for accurate prediction of aerosol optical properties, because the conventional representation cannot separately treat BC-containing and BC-free particles in each size section. The evaluation also shows that BC-containing particles having 55% and 83% of the BC mass can act as CCN at a supersaturation of 0.05% when they leave the source region and after transport for half a day, respectively. These results suggest the importance of the uplifting of BC particles from the PBL near source regions for their efficient long-range transport in the free troposphere. Results from comparisons with aerosol optical measurements conducted during various campaigns, such as the Asian Aerosol Characterization Experiment (ACE Asia) and the Indian Ocean Experiment (INDOEX), suggest that MADRID-BC simulations can capture general features of aerosol optical properties in outflow from anthropogenic sources.

Accumulation of Amyloid β-Protein in the Low-Density Membrane Domain Accurately Reflects the Extent of β-Amyloid Deposition in the Brain

To learn more about the process of amyloid β-protein (Aβ) deposition in the brain, human prefrontal cortices were fractionated by sucrose density gradient centrifugation, and the Aβ content in each fraction was quantified by a two-site enzyme-linked immunosorbent assay. The fractionation protocol revealed two pools of insoluble Aβ. One corresponded to a low-density membrane domain; the other was primarily composed of extracellular Aβ deposits in those cases in which Aβ accumulated to significant levels. Aβ42 levels in the low-density membrane domain were proportional to the extent of total Aβ42 accumulation, which is known to correlate well with overall amyloid burden. In PDAPP mice that form senile plaques and accumulate Aβ in a similar manner to aging humans, Aβ42 accumulation in the low-density membrane domain also increased as Aβ deposition progressed with aging. These observations indicate that the Aβ42 associated with low-density membrane domains is tightly coupled with the process of extracellular Aβ deposition.