Impact of Neuroprotection on Incidence of Alzheimer's Disease

Converging evidence suggests that high levels of education and intellectual activity increase the cognitive reserve and reduce the risk of dementia. However, little is known about the impact that different neuroprotective strategies may have on the incidence of Alzheimer's disease. Using a simple mathematical regression model, it is shown here that age-specific counts of basic cognitive units (surrogate of neurons or synapses) in the normal population can be estimated from Alzheimer's incidence rates. Hence, the model can be used to test the effect of neuroprotection on Alzheimer's incidence. It was found that the number of basic cognitive units decreases with age, but levels off in older people. There were no gender differences after correcting for survival. The model shows that even modest neuroprotective effects on basic cognitive units can lead to dramatic reductions in the number of Alzheimer's cases. Most remarkably, a 5% increase in the cognitive reserve would prevent one third of Alzheimer's cases. These results suggest that public health policies aimed at increasing the cognitive reserve in the general population (e.g., implementing higher levels of education) are likely the most effective strategy for preventing Alzheimer's disease

Lipid Raft Size and Lipid Mobility in Non-raft Domains Increase during Aging and Are Exacerbated in APP/PS1 Mice Model of Alzheimer's Disease. Predictions from an Agent-Based Mathematical Model

A connection between lipid rafts and Alzheimer's disease has been studied during the last decades. Mathematical modeling approaches have recently been used to correlate the effects of lipid composition changes in the physicochemical properties of raft-like membranes. Here we propose an agent based model to assess the effect of lipid changes in lipid rafts on the evolution and progression of Alzheimer's disease using lipid profile data obtained in an established model of familial Alzheimer's disease. We have observed that lipid raft size and lipid mobility in non-raft domains are two main factors that increase during age and are accelerated in the transgenic Alzheimer's disease mouse model. The consequences of these changes are discussed in the context of neurotoxic amyloid β production. Our agent based model predicts that increasing sterols (mainly cholesterol) and long-chain polyunsaturated fatty acids (LCPUFA) (mainly DHA, docosahexaenoic acid) proportions in the membrane composition might delay the onset and progression of the disease.This work was funded by research grants from BIO2014-54411-C2-2-R and SAF2014-52582-R from Ministerio de Economía y Competitividad (MINECO, Spain). GSR acknowledges the support of Obra Social La Caixa-Fundación CajaCanarias that granted him a Posgraduate Fellowship at the Universidad de La Laguna.Peer reviewedPeer Reviewe

Early Diagnosis of Alzheimer's disease by NIRF Spectroscopy and Nuclear Medicine-v.4.0

There is an urgent need for the early detection of diseases such as Alzheimer’s (AD) and Cancers in order to enable their successful treatment. Cancer is the second major cause of death after Heart Disease, and AD is the third major cause of death with major, human and financial/economics trillion dollar consequences for the society. Nuclear Medicine is concerned with applications in Medicine of Nuclear Science and Engineering techniques and knowledge. Three major Nuclear Medicine techniques that are established for diagnostic and research purposes are: Positron Emission Tomography (PET) and CAT/CT, Nuclear Magnetic Resonance Imaging (NMRI/MRI). However, these three techniques have also major limitations in terms of either cost or image resolution, as well as patient irradiation in the case of CAT/CT and PET. On the other hand, Near Infrared Chemical Imaging Microspectroscopy and certain Fluorescence spectroscopic techniques are capable of single cancer cell and/or single molecule detection and/or imaging. Such powerful capabilities, combined with low cost of diagnostics, make these novel techniques very attractive means for early detection of diseases such as cancer and Alzheimer’s, that are promising to reduce the fatality rate of patients through adequate diagnosis and treatment of such diseases at early stages. 
Currently NIH provides only inadequate funding for the clinical and research aspects of these novel investigation and clinical diagnostic techniques by FT-NIRS and Fluorescence spectrocopy for early detection of Alzheimer’s and Cancers.
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Early Diagnosis of Alzheimer's disease by NIRF Spectroscopy and Nuclear Medicine

There is an urgent need for the early detection of diseases such as Alzheimer’s (AD) and Cancers in order to enable their successful treatment. Cancer is the second major cause of death after Heart Disease, and AD is the third major cause of death with major, human and financial/economics trillion dollar consequences for the society. Nuclear Medicine is concerned with applications in Medicine of Nuclear Science and Engineering techniques and knowledge. Three major Nuclear Medicine techniques that are established for diagnostic and research purposes are: Positron Emission Tomography (PET) and CAT/CT, Nuclear Magnetic Resonance Imaging (NMRI/MRI). However, these three techniques have also major limitations in terms of either cost or image resolution, as well as patient irradiation in the case of CAT/CT and PET. On the other hand, Near Infrared Chemical Imaging Microspectroscopy and certain Fluorescence spectroscopic techniques are capable of single cancer cell and/or single molecule detection and/or imaging. Such powerful capabilities, combined with low cost of diagnostics, make these novel techniques very attractive means for early detection of diseases such as cancer and Alzheimer’s, that are promising to reduce the fatality rate of patients through adequate diagnosis and treatment of such diseases at early stages. 
Currently NIH provides only inadequate funding for the clinical and research aspects of these novel investigation and clinical diagnostic techniques by FT-NIRS and Fluorescence spectrocopy for early detection of Alzheimer's and Cancers

Early Diagnosis of Alzheimer's Disease by NIRF Spectroscopy\ud and Nuclear Medicine\ud

Novel approaches to Early Diagnosis of Alzheimer's Disease by NIRF Spectroscopy and Nuclear Medicine are presented and related cognitive, as well as molecular and cellular, models are critically evaluated.\u

Neurodegeneration: Potential Causes, Prevention, and Future Treatment Options

Here I advance a hypothesis that neurodegeneration is a natural process associated with aging due to the loss of genetic redundancy following a mathematical model R(t) = R0(1-αe(βC+γI+δEt)t), where the calorie intake (C) and immune response (I) play critical roles. The early onset of neurodegenerative diseases such as Alzheimer’s disease is due to metabolic imbalance or chronic immune reactions to various infections. Therefore, the potential treatment options for neurodegenerative diseases are to modulate metabolism and immune response

Current advances in systems and integrative biology

Systems biology has gained a tremendous amount of interest in the last few years. This is partly due to the realization that traditional approaches focusing only on a few molecules at a time cannot describe the impact of aberrant or modulated molecular environments across a whole system. Furthermore, a hypothesis-driven study aims to prove or disprove its postulations, whereas a hypothesis-free systems approach can yield an unbiased and novel testable hypothesis as an end-result. This latter approach foregoes assumptions which predict how a biological system should react to an altered microenvironment within a cellular context, across a tissue or impacting on distant organs. Additionally, re-use of existing data by systematic data mining and re-stratification, one of the cornerstones of integrative systems biology, is also gaining attention. While tremendous efforts using a systems methodology have already yielded excellent results, it is apparent that a lack of suitable analytic tools and purpose-built databases poses a major bottleneck in applying a systematic workflow. This review addresses the current approaches used in systems analysis and obstacles often encountered in large-scale data analysis and integration which tend to go unnoticed, but have a direct impact on the final outcome of a systems approach. Its wide applicability, ranging from basic research, disease descriptors, pharmacological studies, to personalized medicine, makes this emerging approach well suited to address biological and medical questions where conventional methods are not ideal

Well-posedness of a mathematical model for Alzheimer's disease

We consider the existence and uniqueness of solutions of an initial-boundary value problem for a coupled system of PDE's arising in a model for Alzheimer's disease. Apart from reaction diffusion equations, the system contains a transport equation in a bounded interval for a probability measure which is related to the malfunctioning of neurons. The main ingredients to prove existence are: the method of characteristics for the transport equation, a priori estimates for solutions of the reaction diffusion equations, a variant of the classical contraction theorem, and the Wasserstein metric for the part concerning the probability measure. We stress that all hypotheses on the data are not suggested by mathematical artefacts, but are naturally imposed by modelling considerations. In particular the use of a probability measure is natural from a modelling point of view. The nontrivial part of the analysis is the suitable combination of the various mathematical tools, which is not quite routine and requires various technical adjustments