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The pathology of late-onset Alzheimer’s disease (LOAD) is still poorly understood, but it is multifactorial and closely related to changes with aging. We developed a cellular platform for collecting skin fibroblasts or blood cells from LOAD patients and non-demented control individuals, which are then used in an induced pluripotent stem cell (iPSC) paradigm to produce brain cells for determining LOAD pathogenic processes in the context of age, disease, genetic background, cell development, and cell type. This model has provided evidence for an innate inefficient cellular energy management in LOAD that is associated with alterations of cellular transcriptomes and lipid compositions, and interconnected cause-and-effect linkages, such as impaired insulin/IGF-1 signaling, bioenergetic substrate deficiencies, diminished glucose metabolism, and disruption of autophagic flux, among others. In addition, a testing of compounds revealed some restoration of these altered bioenergetic and metabolic processes in LOAD cells. Altogether, our studies have identified an inherent LOAD-associated cellular metabolic phenotype as a potential risk factor for developing neurodegenerative diseases with aging. We propose that our cellular model allows for patient-oriented examination of numerous mechanisms and interactions in LOAD pathogenesis, which can be used as a basis for a personalized medicine approach to predict altered aging and risk of developing dementia, and to test or implement (customized) therapeutic or disease-preventive intervention strategies.

Brain function, the brain's metabolic activity, cerebral blood flow (CBF), and intracranial pressure are intimately linked within the tightly autoregulated regime of intracranial physiology in which the role of tissue viscoelasticity remains elusive. We applied multifrequency magnetic resonance elastography (MRE) paired with CBF measurements in 14 healthy subjects exposed to 5-min carbon dioxide-enriched breathing air to induce cerebral vasodilatation by hypercapnia. Stiffness and viscosity as quantified by the magnitude and phase angle of the complex shear modulus, | G *| and ϕ , as well as CBF of the whole brain and 25 gray matter sub-regions were analyzed prior to, during, and after hypercapnia. In all subjects, whole-brain stiffness and viscosity increased due to hypercapnia by 3.3 ± 1.9% and 2.0 ± 1.1% which was accompanied by a CBF increase of 36 ± 15%. Post-hypercapnia, | G *| and ϕ reduced to normal values while CBF decreased by 13 ± 15% below baseline. Hypercapnia-induced viscosity changes correlated with CBF changes, whereas stiffness changes did not. The MRE-measured viscosity changes correlated with blood viscosity changes predicted by the Fåhræus-Lindqvist model and microvessel diameter changes from the literature. Our results suggest that brain viscoelastic properties are influenced by microvessel blood flow and blood viscosity: vasodilatation and increased blood viscosity due to hypercapnia result in an increase in MRE values related to viscosity.

Background: The Accra climate change talks held from 21-27 August 2008 in Accra, Ghana, were part of an ongoing series of meetings leading up to the Copenhagen meeting in December 2009. During the meeting a set of options for accounting carbon sequestration in forestry on a post-2012 framework was presented. The options include gross-net and net-net accounting and approaches for establishing baselines., Results: This article demonstrates the embedded consequences of Accra Accounting Options for the case study of German national GHG accounting. It presents the most current assessment of sequestration rates by forest management for the period 1990 - 2007, provides an outlook of future emissions and removals (up to the year 2042) as related to three different management scenarios, and shows that implementation of some Accra options may reverse sources to sinks, or sinks to sources., Conclusion: The results of the study highlight the importance of elaborating an accounting system that would prioritize the climate convention goals, not national preferences.