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Alzheimer's etiologies

Daniel V Guebel, Néstor V Torres
Motivation: In the brain of elderly-healthy individuals, the effects of sexual dimorphism and those due to normal aging appear overlapped. Discrimination of these two dimensions would powerfully contribute to a better understanding of the etiology of some neurodegenerative diseases, such as "sporadic" Alzheimer. Methods: Following a system biology approach, top-down and bottom-up strategies were combined. First, public transcriptome data corresponding to the transition from adulthood to the aging stage in normal, human hippocampus were analyzed through an optimized microarray post-processing (Q-GDEMAR method) together with a proper experimental design (full factorial analysis)...
2016: Frontiers in Aging Neuroscience
Salma Jamal, Sukriti Goyal, Asheesh Shanker, Abhinav Grover
BACKGROUND: Alzheimer's disease (AD) is a complex progressive neurodegenerative disorder commonly characterized by short term memory loss. Presently no effective therapeutic treatments exist that can completely cure this disease. The cause of Alzheimer's is still unclear, however one of the other major factors involved in AD pathogenesis are the genetic factors and around 70 % risk of the disease is assumed to be due to the large number of genes involved. Although genetic association studies have revealed a number of potential AD susceptibility genes, there still exists a need for identification of unidentified AD-associated genes and therapeutic targets to have better understanding of the disease-causing mechanisms of Alzheimer's towards development of effective AD therapeutics...
October 18, 2016: BMC Genomics
Seong-Tshool Hong
The human intestine contains a massive and complex microbial community called gut microbiota. A typical human carries 100 trillion microbes in his/her body which is 10 times greater than the number of their host cells, i.e. whole number of human cells. A combined microbial genome constituting gut microbiota is well excess our own human genome. The microbial composition of gut microbiotata and its role on diseases became a booming area of research, presenting a new paradigm of opportunities for modern medicines...
September 2016: Journal of Hypertension
Leroy L Cooper, Gary F Mitchell
BACKGROUND: Aortic stiffness is associated with cardiovascular and cerebrovascular events and cognitive decline. This mini-review focuses on relations of aortic stiffness with microvascular dysfunction and discusses the contribution of abnormal pulsatile hemodynamics to cerebrovascular damage and cognitive decline. We also provide a rationale for considering aortic stiffness as a putative and important contributor to memory impairment in older individuals. SUMMARY: Aging is associated with stiffening of the aorta but not the muscular arteries, which reduces wave reflection and increases the transmission of pulsatility into the periphery...
September 2016: Pulse (Basel, Switzerland)
Christopher Rohde, Esben Agerbo, Philip Rising Nielsen
Increased prevalence of lifestyle risk factors or shared etiology may underlie the association between schizophrenia and the subsequent risk of dementia. We explored the association between having a spouse with schizophrenia and the risk of dementia. We found a positive relationship between having a spouse with schizophrenia and vascular dementia in individuals without a mental disorder themselves but no association between having a spouse with schizophrenia and Alzheimer's dementia. As spouses share environmental risk factors and lifestyle, this might suggest that the excess risk of dementia in probands with schizophrenia could be ascribed to the unhealthy living environment among individuals with schizophrenia...
October 15, 2016: Social Psychiatry and Psychiatric Epidemiology
Gennady V Roshchupkin, Hieab H Adams, Sven J van der Lee, Meike W Vernooij, Cornelia M van Duijn, Andre G Uitterlinden, Aad van der Lugt, Albert Hofman, Wiro J Niessen, Mohammad A Ikram
The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions...
September 4, 2016: Neurobiology of Aging
Willemijn J Jansen, Ron L H Handels, Pieter Jelle Visser, Pauline Aalten, Femke Bouwman, Jurgen Claassen, Peter van Domburg, Erik Hoff, Jan Hoogmoed, Albert F G Leentjens, Marcel Olde Rikkert, Ania M Oleksik, Machiel Smid, Philip Scheltens, Claire Wolfs, Frans Verhey, Inez H G B Ramakers
BACKGROUND: Neuropsychological testing has long been embedded in daily clinical practice at memory clinics but the added value of a complete neuropsychological assessment (NPA) to standard clinical evaluation is unknown. OBJECTIVE: To evaluate the added diagnostic and prognostic value of NPA to clinical evaluation only in memory clinic patients. METHODS: In 221 memory clinic patients of a prospective cohort study, clinical experts diagnosed clinical syndrome (subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or dementia) and etiology (Alzheimer's disease (AD) or no AD), and provided a prognosis of disease course (decline or no decline) before and after results of NPA were made available...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Thangavelu Soundara Rajan, Domenico Scionti, Francesca Diomede, Gianpaolo Grassi, Federica Pollastro, Adriano Piattelli, Lucio Cocco, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
Research in recent years has extensively investigated the therapeutic efficacy of mesenchymal stromal cells in regenerative medicine for many neurodegenerative diseases at preclinical and clinical stages. However, the success rate of stem cell therapy remains less at translational phase. Lack of relevant animal models that potentially simulate the molecular etiology of human pathological symptoms might be a reason behind such poor clinical outcomes associated with stem cell therapy. Apparently, self-renewal and differentiation ability of mesenchymal stem cells may help to study the early developmental signaling pathways connected with the diseases, such as Alzheimer's disease, Amyotrophic lateral sclerosis (ALS), etc...
October 7, 2016: Journal of Cellular Biochemistry
M Rodríguez-Arribas, S M S Yakhine-Diop, J M Bravo-San Pedro, P Gómez-Suaga, R Gómez-Sánchez, G Martínez-Chacón, J M Fuentes, R A González-Polo, M Niso-Santano
Mitochondria-associated membranes (MAMs) are structures that regulate physiological functions between endoplasmic reticulum (ER) and mitochondria in order to maintain calcium signaling and mitochondrial biogenesis. Several proteins located in MAMs, including those encoded by PARK genes and some of neurodegeneration-related proteins (huntingtin, presenilin, etc.), ensure this regulation. In this regard, MAM alteration is associated with neurodegenerative diseases such as Parkinson's (PD), Alzheimer's (AD), and Huntington's diseases (HD) and contributes to the appearance of the pathogenesis features, i...
October 6, 2016: Molecular Neurobiology
Julian Little, Caroline Barakat-Haddad, Rosemary Martino, Tamara Pringsheim, Helen Tremlett, Kyla A McKay, Pascal van Lieshout, Stephanie J Walsh, James Gomes, Daniel Krewski
This paper presents an overview of genetic variation associated with the onset and progression of 14 neurological disorders, focusing primarily on association studies. The 14 disorders are heterogeneous in terms of their frequency, age of onset, etiology and progression. There is substantially less evidence on progression than onset. With regard to onset, the conditions are diverse in terms of their epidemiology and patterns of familial aggregation. While the muscular dystrophies and Huntington's disease are monogenic diseases, for the other 12 conditions only a small proportion of cases is associated with specific genetic syndromes or mutations...
October 3, 2016: Neurotoxicology
Marzena Ułamek-Kozioł, Ryszard Pluta, Sławomir Januszewski, Janusz Kocki, Anna Bogucka-Kocka, Stanisław J Czuczwar
We review the Alzheimer-related expression of genes following brain ischemia as risk factors for late-onset of sporadic Alzheimer's disease and their role in Alzheimer's disease ischemia-reperfusion pathogenesis. More recent advances in understanding ischemic etiology of Alzheimer's disease have revealed dysregulation of Alzheimer-associated genes including amyloid protein precursor, β-secretase, presenilin 1 and 2, autophagy, mitophagy and apoptosis. We review the relationship between these genes dysregulated by brain ischemia and the cellular and neuropathological characteristics of Alzheimer's disease...
September 5, 2016: Pharmacological Reports: PR
Syeda Mehpara Farhat, Aamra Mahboob, Ghazala Iqbal, Touqeer Ahmed
Aluminum is associated with etiology of many neurodegenerative diseases specially Alzheimer's disease. Chronic exposure to aluminum via drinking water results in aluminum deposition in the brain that leads to cognitive deficits. The study aimed to determine the effects of aluminum on cholinergic biomarkers, i.e., acetylcholine level, free choline level, and choline acetyltransferase gene expression, and how cholinergic deficit affects novel object recognition and sociability in mice. Mice were treated with AlCl3 (250 mg/kg)...
October 6, 2016: Biological Trace Element Research
Christopher Rohde, Esben Agerbo, Philip Rising Nielsen
BACKGROUND/AIMS: Prior studies have consistently found a higher risk of dementia in individuals with schizophrenia, but whether this is due to a common etiology between the disorders remains obscure. We wanted to elucidate this association by investigating whether schizophrenia in offspring increases the risk of Alzheimer's dementia. METHODS: All individuals born between 1930 and 1953 were identified through national registers and followed from their 50th birthday until the date of Alzheimer's dementia, death or end of the study...
May 2016: Dementia and Geriatric Cognitive Disorders Extra
Xing Peng, Peiqi Xing, Xiuhui Li, Ying Qian, Fuhai Song, Zhouxian Bai, Guangchun Han, Hongxing Lei
Alzheimer's disease (AD) remains to be a grand challenge for the international community despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripotent cells (iPSCs)...
September 28, 2016: Genomics, Proteomics & Bioinformatics
Keith Rubin, Steven Glazer
While a number of endogenous risk factors including age and genetics are established for Alzheimer's disease (AD), identification of acquired, potentially preventable or treatable causes, remains limited. In this paper, we review three epidemiologic case studies and present extensive biologic, immunologic and anatomic evidence to support a novel hypothesis that Bordetella pertussis (BP), the bacterium better known to cause whooping cough, is an important potential cause of AD. Cross-cultural documentation of nasopharyngeal subclinical BP colonization reflecting BP-specific mucosal immunodeficiency, proximate anatomy of intranasal mucosal surfaces to central nervous system (CNS) olfactory pathways, and mechanisms by which BP and BP toxin account for all hallmark pathology of AD are reviewed, substantiating biologic plausibility...
September 28, 2016: Immunobiology
X T Li, D F Cai
Parkinson's disease(PD)was the second most common neurodegenerative disorder after Alzheimer's disease. Incidence of PD was ascending year by year. The etiology of PD is poorly understood, involving aging, genetic and environmental factors. Recently, environmental compound had attracted more and more research interest. Studies and extrapolation from epidemiology, animal experiments and cell culture suggested that environmental compound had involved in the molecular mechanisms including mitochondrial dysfunction, oxidative stress, microglia activation, abnormal aggregation of α-synuclein and autophagy damage ,which seemed to increase PD risk...
October 6, 2016: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Bruno Alies, Amandine Conte-Daban, Stéphanie Sayen, Fabrice Collin, Isabelle Kieffer, Emmanuel Guillon, Peter Faller, Christelle Hureau
The Zn(II) ion has been linked to Alzheimer's disease (AD) due to its ability to modulate the aggregating properties of the amyloid-β (Aβ) peptide, where Aβ aggregation is a central event in the etiology of the disease. Delineating Zn(II) binding properties to Aβ is thus a prerequisite to better grasp its potential role in AD. Because of (i) the flexibility of the Aβ peptide, (ii) the multiplicity of anchoring sites, and (iii) the silent nature of the Zn(II) ion in most classical spectroscopies, this is a difficult task...
October 17, 2016: Inorganic Chemistry
Sonia Marcone, Jean-François Gagnon, Sarah Lecomte, Hélène Imbeault, Frédérique Limoges, Ronald B Postuma, Josie-Anne Bertrand, Sven Joubert, Isabelle Rouleau
OBJECTIVE: Prospective memory (PM) is a cognitive function defined as the ability to perform an intention at an appropriate moment in the future. In the aging population, PM is essential for maintaining independent daily living. Introduced as a simple and quick way to assess PM in clinical settings, the envelope task has to date received very limited empirical and practical interest. METHODS: The present study investigated the task's clinical utility in detecting PM impairment in a sample composed of 49 healthy older adults (OA), 41 patients with Alzheimer's disease, and 64 individuals with amnestic and nonamnestic mild cognitive impairment (MCI) of heterogeneous etiology: 17 of idiopathic nature, 20 presenting an idiopathic rapid-eye movement sleep behaviour disorder, and 27 patients diagnosed with idiopathic Parkinson's disease...
September 26, 2016: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
Vittorio Calabrese, James Giordano, Anna Signorile, Maria Laura Ontario, Sergio Castorina, Concetta De Pasquale, Gunter Eckert, Edward J Calabrese
Vascular dementia (VaD), considered the second most common cause of cognitive impairment after Alzheimer disease in the elderly, involves the impairment of memory and cognitive function as a consequence of cerebrovascular disease. Chronic cerebral hypoperfusion is a common pathophysiological condition frequently occurring in VaD. It is generally associated with neurovascular degeneration, in which neuronal damage and blood-brain barrier alterations coexist and evoke beta-amyloid-induced oxidative and nitrosative stress, mitochondrial dysfunction, and inflammasome- promoted neuroinflammation, which contribute to and exacerbate the course of disease...
December 2016: Journal of Neuroscience Research
Rui Wang, P Hemachandra Reddy
Excitatory glutamatergic neurotransmission via N-methyl-d-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. However, excessive NMDAR activity causes excitotoxicity and promotes cell death, underlying a potential mechanism of neurodegeneration occurred in Alzheimer's disease (AD). Studies indicate that the distinct outcomes of NMDAR-mediated responses are induced by regionalized receptor activities, followed by different downstream signaling pathways. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival...
September 23, 2016: Journal of Alzheimer's Disease: JAD
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