High-Fat and Cholesterol Intake Affects Brain Homeostasis and Could Accelerate the Development of Dementia: A Systemic View

Alzheimer’s disease is the most common type of dementia in occidental countries. The majority of the cases develop the disease for no genetic reasons; therefore, it is crucial to establish which environmental factors trigger the development of the disease. It has been proposed that nutritional habits, especially main components of Western countries’ diet such as saturated fat or cholesterol, increase the risk for development of Alzheimer’s disease (AD) and/or accelerate the onset of the disease, which is a big concern in countries where obesity is a public health problem. It is crucial to understand the links between alimentary habits and the development of AD and other types of dementia. A possible mechanism is the disruption of blood–brain barrier (BBB), which is the protection of the brain from circulating blood. Such disruptions can result from consuming high-fat diet (HFD) or high-cholesterol diet (HCD) and inflammation produced by alteration in brain vasculature resulted for chronic consumption of such type of diets. What has named a "Systemic view" comprises the idea that; what happens outside of the brain environment does affect brain functioning and the modifications experienced in the brain environment resulted from the influence of external factors will affect the entire body. In the current chapter, we will review the state of the art in the studies of the impact of a diet rich in fat or cholesterol on the brain and how the alterations induced in other organs can impact brain functioning increasing the susceptibility of development of dementia

Editorial: Neurodegeneration: from Genetics to Molecules

Chronic degenerative diseases are one of the major public health problems, particularly those affecting the nervous system. They are characterized by the degeneration of specific cell populations that include several pathologies which contribute significantly to morbidity and mortality in the elderly population. Therefore, in recent years, the study of neuroscience has gained significant importance. Most of these neurodegenerative disorders are the result of a complex interaction between genetic and environmental factors that generate progression and can even determine its severity. The presence of mutations in genes as LRRK2, SNCA, PARK7, PARK2 or PINK1 is associated with Parkinson's disease. Mutations in genes such as APP, PS1 and PS2 are associated with familial Alzheimer's disease; while HTT gene mutations are the cause of Huntington's disease. In most cases, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. It is known that these mutations can also alter the proteins function; however, it has not yet been possible to fully understand how some genetic changes cause the disease or influence the risk of developing these disorders. Most symptoms seen in these conditions occurs when specific nerve cells are damaged or die generating a loss in brain communication. Also many of these mutations generate aggregation of intracellular or extracellular proteins affecting cell function and eventually causing neuronal death. It is unclear whether the presence of these aggregates play an important role in nerve cell death during the development of neurodegenerative diseases, or if they are simply part of the response of cells to the disease. Other mutations affect the mitochondrial function generating alterations in energy production and promoting the formation of unstable molecules such as free radicals. Under normal conditions, the harmful effects caused by free radicals, are offset within the cell. However, in pathological conditions, the presence of mutations can alter this process by allowing the accumulation of radicals and damaging or killing cells. On the other hand, we also know that these diseases may not have a direct genetic component, thus, the study of sporadic type neurodegenerative diseases is much more complex. Histopathological lesions as well as the cellular and molecular alterations are generally indistinguishable from familial cases. For this reason, it is important to understand the genetic and molecular mechanisms associated with this type of pathologies. In this sense, this issue aims to understand the molecular processes that occur in the brain, and how these are influenced by the environment, genetics and behavior

Clinical Association of White Matter Hyperintensities Localization in a Mexican Family with Spastic Paraparesis Carrying the PSEN1 A431E Mutation

Presenilin 1 gene (PSEN1) mutations are the most common cause of familial Alzheimer’s disease (FAD). One of the most abundant FAD mutations, PSEN1 A431E, has been reported to be associated with spastic paraparesis in about half of its carriers, but the determining mechanisms of this phenotype are still unknown. In our study we characterized three A431E mutation carriers, one symptomatic and two asymptomatic, from a Mexican family with a history of spastic paraparesis in all of its affected members. At cognitive assessment and MRI, the symptomatic subject showed an atypical non-amnestic mild cognitive impairment with visuospatial deficits, olfactory dysfunction and significant parieto-occipital brain atrophy. Furthermore, we found several periventricular white matter hyperintensities whose progression pattern and localization correlated with their motor impairment, cognitive profile, and non-motor symptoms. Together, our data suggests that in this family the A431E mutation leads to a divergent neurological disorder in which cognitive deterioration was clinically exceeded by motor impairment and that it involves early glial and vascular pathological changes

Effect of new generation enzymes addition on the physical, viscoelastic and textural properties of traditional Mexican sweet bread

Se estudio el efecto de la adición de enzimas en las propiedades viscosas y texturales de un pan tradicional mexicano.The effect of adding new generation enzymes (0.25, 0.5, 0.75, and 1.0% w/w) on traditional Mexican sweet bread physical, viscoelastic (elastic and plastic work) and textural properties was studied. Physical properties as weight lost, pore uniformity, color, etc., improved with enzyme addition. Viscoelasticity properties were analyzed by uniaxial compression test under small strain, showing that the use of small enzyme fractions (~0.25-0.5% w/w) are enough to enhance mechanical behavior (higher elastic work) and cohesiveness and resilience parameters after four storage days. This trend suggests a mechanism related to pore distribution and an equilibrium crust-crumb that lead to improved bread freshness over storage period. Overall, results indicated that relatively low enzyme concentrations can led to important improvements in the fabrication process of traditional Mexican sweet bread. The proposed enzyme concentrations are as small as 0.25-0.3% w/w, corresponding to approximately half the percentage of the amount frequently used in industrial bread production

The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease

Acknowledgements: Authors want to express their gratitude to Dr. P. Davies (Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder (NorthWestern, Chicago, IL, USA) for the generous gift of mAbs (TG-3, Alz-50, and MC1), and (TauC-3), respectively, and to M. en C. Ivan J. Galván-Mendoza for his support in confocal microscopy, and Ms. Maricarmen De Lorenz for her secretarial assistance. We also want to express our gratitude to the Mexican Families who donate the brain of their loved ones affected with Alzheimer's disease, and made possible our research. This work was financially supported by CONACyT grant, No. 142293 (For R.M).Peer reviewedPublisher PD

Genetic analysis of 17 Y-STRs in a Mestizo population from the Central Valley of Mexico

This study aims to portray the complex diversity of the Mexican Mestizo population, which represents 98.8% of the entire population of Mexico. We compiled extended haplotype data of the Y chromosome from populations in the Central Valley of Mexico (CVM), which were compared to other Mestizo and parental (Amerindian, European and African) populations. A complex ancestral relationship was found in the CVM population, suggesting cosmopolitan origins. Nevertheless, the most preeminent lineages point towards a European ancestry, where the R1b was the most frequent. In addition, important frequencies of Amerindian linages were also found in the Mestizo sample studied. Interestingly, the Amerindian ancestry showed a remarkable substructure, which was represented by the two main founding lineages: QL54 (x M3) and M3. However, even within each lineage a high diversity was found despite the small number of samples bearers of these lineages. Further, we detected important genetic differences between the CVM populations and the Mexican Mestizo populations from the north and south. This result points to the fact that Mestizo populations present different ancestral proportions, which are related to the demographic events that gave origin to each population. Finally, we provide additional forensic statistical parameters that are useful in the interpretation of genetic analysis where autosomal loci are limited. Our findings illustrate the complex genetic background of the Mexican Mestizo population and reinforce the need to encompass more geographic regions to generate more robust data for forensic applications

Alzheimer’s Disease and Type 2 Diabetes Mellitus: Molecular Mechanisms and Similarities

Alzheimer’s disease (AD) has become one of the most threatening diseases in the elderly, and type 2 diabetes mellitus (T2DM) is a major health problem in the world, representing 7.4% of the population. Several studies have produced epidemiological, clinical, and pathological evidence of the relationship between AD and T2DM. Laboratory research using animal models has identified mechanisms shared by both T2DM and AD. Particularly, there is an increase of tau phosphorylation and cleavage, which is known to be particularly toxic to neurons and to form a nucleation for neurofibrillary tangles. Also, alterations in synaptic plasticity are associated to tau pathology through the direct abnormal interaction of pathological tau with synaptic proteins and indirectly through Tau-activated neuroinflammatory processes. Many T2DM complications are potentiated or initiated by the accumulation of specific forms of advanced glycation end products (AGEs) and their interaction with its receptors (RAGE). AGEs promote β-amyloid aggregation and cytotoxicity, while glycation of tau may enhance their aggregation. Therefore, this review addresses the analysis of the common mechanisms where the major molecular players of these two diseases participate and contribute to a better understanding of these diseases in their pathogenic relationship