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Alzheimer's etiologies

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https://www.readbyqxmd.com/read/27909447/stem-cell-therapy-a-prospective-treatment-for-alzheimer-s-disease
#1
REVIEW
Ji Han Lee, Il-Hoan Oh, Hyun Kook Lim
Alzheimer's disease (AD) without cure remains as a serious health issue in the modern society. The major neuropathological alterations in AD are characterized by chronic neuroinflammation and neuronal loss due to neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau, plaques of β-amyloid (Aβ) and various metabolic dysfunctions. Due to the multifaceted nature of AD pathology and our limited understanding on its etiology, AD is difficult to be treated with currently available pharmaceuticals...
November 2016: Psychiatry Investigation
https://www.readbyqxmd.com/read/27895577/fus1-ko-mouse-as-a-model-of-oxidative-stress-mediated-sporadic-alzheimer-s-disease-circadian-disruption-and-long-term-spatial-and-olfactory-memory-impairments
#2
Guillermo Coronas-Samano, Keeley L Baker, Winston J T Tan, Alla V Ivanova, Justus V Verhagen
Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27889432/decrease-of-high-voltage-ca-2-currents-in-the-dentate-gyrus-granule-cells-by-entorhinal-amyloidopathy-is-reversed-by-calcium-channel-blockade
#3
Hamid Gholami Pourbadie, Nima Naderi, Hadi Mirzapour Delavar, Mahshid Hosseinzadeh, Nasrin Mehranfard, Fariba Khodagholi, Mahyar Janahmadi, Fereshteh Motamedi
In the Alzheimer's disease (AD), entorhinal-hippocampal circuit is one of the earliest affected networks. There are some evidences indicating abnormal neuronal excitability and impaired synaptic plasticity in the dentate gyrus (DG) of AD animal model. However, the underlying mechanism leading to DG dysfunction particularly in the early phase of AD is not known. Since calcium dyshomeostasis has a critical role in the etiology of AD, it is possible that this phenomenon precedes electrophysiological alteration in the DG...
November 24, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27878426/the-differential-effects-of-alzheimer-s-disease-and-lewy-body-pathology-on-cognitive-performance-a-meta-analysis
#4
REVIEW
Ashita S Gurnani, Brandon E Gavett
Differential diagnosis of Alzheimer's disease (AD) from normal aging and other dementia etiologies is imperative for disease specific treatment options and long-term care planning. Neuropathological confirmation is the gold standard for neurodegenerative disease diagnosis, yet most published studies examining the use of neuropsychological tests in the differential diagnosis of dementia rely upon clinical diagnostic outcomes. The present study undertook a meta-analytic review of the literature to identify cognitive tests and domains that allow for the differentiation of individuals with AD pathology from individuals with dementia with Lewy Bodies (DLB) pathology and pathology-free individuals...
November 22, 2016: Neuropsychology Review
https://www.readbyqxmd.com/read/27875990/inverse-relationship-between-alzheimer-s-disease-and-cancer-and-other-factors-contributing-to-alzheimer-s-disease-a-systematic-review
#5
Ovais Shafi
BACKGROUND: The AD etiology is yet not properly known. Interactions among environmental factors, multiple susceptibility genes and aging, contribute to AD. This study investigates the factors that play role in causing AD and how changes in cellular pathways contribute to AD. METHODS: PUBMED database, MEDLINE database and Google Scholar were searched with no date restrictions for published articles involving cellular pathways with roles in cancers, cell survival, growth, proliferation, development, aging, and also contributing to Alzheimer's disease...
November 22, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27875954/how-immune-inflammatory-processes-link-cns-and-psychiatric-disorders-classification-and-treatment-implications
#6
George Anderson, Michael Maes
In this article the emerging biological overlaps of CNS disorders and psychiatric conditions are reviewed. Recent work has highlighted how immune-inflammatory processes and their interactions with oxidative and nitrosative stress, couple to drive changes in neuroregulatory tryptophan catabolites, with consequences for serotonin availability, including as a precursor for the melatonergic pathways. Subsequent alterations in the regulation of local melatonin synthesis are likely to have direct impacts on the reactivity of immune cells, both centrally and systemically...
November 22, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27858708/cerebrospinal-fluid-biomarkers-as-a-diagnostic-tool-of-the-underlying-pathology-of-primary-progressive-aphasia
#7
George P Paraskevas, Dimitrios Kaselimis, Evie Kourtidou, Vasilios Constantinides, Anastasia Bougea, Costas Potagas, Ioannis Evdokimidis, Elisabeth Kapaki
BACKGROUND: Primary progressive aphasia (PPA) may present with three main clinical variants, namely nonfluent agrammatic (nfaPPA), semantic (sPPA), and logopenic (lPPA) subtypes. Frontotemporal lobar degenerations (FTLD) or Alzheimer's disease (AD) are the most common etiologies. OBJECTIVE: To study the potential of cerebrospinal fluid (CSF) biomarkers for identifying the underlying pathology in patients with PPA. METHODS: CSF levels of total tau protein (τT), amyloid-β peptide (Aβ42), and tau phosphorylated at threonine-181 (τP - 181) were measured by double sandwich, enzyme-linked immunosorbent assay (ELISA) in 43 patients with PPA, 26 patients with AD, and 17 healthy controls...
November 14, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27843444/are-csf-biomarkers-useful-as-prognostic-indicators-in-diagnostically-unresolved-cognitively-impaired-patients-in-a-normal-clinical-setting
#8
Malene Schjønning Nielsen, Anja Hviid Simonsen, Volkert Siersma, Steen Gregers Hasselbalch, Peter Høgh
BACKGROUND: Despite an extensive evaluation program, patients may remain diagnostically unresolved with regard to the etiology of their cognitive dysfunction. Cerebrospinal fluid neuroinflammation and Alzheimer disease (AD) biomarkers may act as indicators of neurodegenerative disorders in diagnostically unresolved patients. METHODS: Data on 348 patients were retrospectively evaluated. All participants had a standardized diagnostic workup and follow-up in a memory clinic...
September 2016: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/27814610/molecular-mechanisms-of-the-genetic-risk-factors-in-pathogenesis-of-alzheimer-disease
#9
Kunihiko Kanatsu, Taisuke Tomita
Alzheimer disease (AD) is a neurodegenerative disease characterized by the extensive deposition of senile plaques and neurofibrillary tangles. Until recently, only the APOE gene had been known as a genetic risk factor for late-onset AD (LOAD), which accounts for more than 95% of all AD cases. However, in addition to this well-established genetic risk factor, genome-wide association studies have identified several single nucleotide polymorphisms as genetic risk factors of LOAD, such as PICALM and BIN1. In addition, whole genome sequencing and exome sequencing have identified rare variants associated with LOAD, including TREM2...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27813127/psychotropic-drug-development-strategies-that-target-neuropsychiatric-etiologies-in-alzheimer-s-and-parkinson-s-diseases
#10
REVIEW
Cornelis J Van der Schyf
Preclinical Research Neuropsychiatric symptoms are currently recognized as a common burden in patients suffering from Alzheimer's disease (AD), Parkinson's disease (PD), and many other neurodegenerative disorders. Earlier theories positing that these symptoms emerge predominantly in patients with late-stage disease have been largely dismissed. It is now generally accepted that many neuropsychiatric symptoms commonly manifest very early in neurodegenerative disease stages, and in many cases are even considered prodromal indicators...
November 4, 2016: Drug Development Research
https://www.readbyqxmd.com/read/27809706/oxidative-stress-and-mitochondrial-dysfunction-linked-neurodegenerative-disorders
#11
Md Torequl Islam
Reactive species play an important role in physiological functions. Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species along with the failure of balance by the body's antioxidant enzyme systems results in destruction of cellular structures, lipids, proteins, and genetic materials such as DNA and RNA. Moreover, the effects of reactive species on mitochondria and their metabolic processes eventually cause a rise in ROS/RNS levels, leading to oxidation of mitochondrial proteins, lipids, and DNA...
November 3, 2016: Neurological Research
https://www.readbyqxmd.com/read/27807285/the-bace1-inhibitor-verubecestat-mk-8931-reduces-cns-%C3%AE-amyloid-in-animal-models-and-in-alzheimer-s-disease-patients
#12
Matthew E Kennedy, Andrew W Stamford, Xia Chen, Kathleen Cox, Jared N Cumming, Marissa F Dockendorf, Michael Egan, Larry Ereshefsky, Robert A Hodgson, Lynn A Hyde, Stanford Jhee, Huub J Kleijn, Reshma Kuvelkar, Wei Li, Britta A Mattson, Hong Mei, John Palcza, Jack D Scott, Michael Tanen, Matthew D Troyer, Jack L Tseng, Julie A Stone, Eric M Parker, Mark S Forman
β-Amyloid (Aβ) peptides are thought to be critically involved in the etiology of Alzheimer's disease (AD). The aspartyl protease β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of Aβ, and BACE1 inhibition is thus an attractive target for the treatment of AD. We show that verubecestat (MK-8931) is a potent, selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of Aβ40, Aβ42, and sAPPβ (a direct product of BACE1 enzymatic activity) after acute and chronic administration to rats and monkeys...
November 2, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27792009/role-of-niemann-pick-type-c-disease-mutations-in-dementia
#13
Chiara Cupidi, Francesca Frangipane, Maura Gallo, Alessandra Clodomiro, Rosanna Colao, Livia Bernardi, Maria Anfossi, Maria Elena Conidi, Franca Vasso, Sabrina Anna Maria Curcio, Maria Mirabelli, Nicoletta Smirne, Giusi Torchia, Maria Gabriella Muraca, Gianfranco Puccio, Raffaele Di Lorenzo, Stefania Zampieri, Milena Romanello, Andrea Dardis, Raffaele Giovanni Maletta, Amalia Cecilia Bruni
BACKGROUND: Several neurological and systemic diseases can cause dementia, beyond Alzheimer's disease. Rare genetic causes are often responsible for dementia with atypical features. Recently, mutations causative for Niemann-Pick type C disease (NPC) have also been implicated in neurodegenerative diseases. NPC is an autosomal recessive lipid storage disorder caused by mutations in NPC1 and NPC2 genes. In adults, clinical presentation mimicking other neurodegenerative diseases makes diagnosis difficult...
October 24, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27789292/role-of-4-hydroxy-2-nonenal-hne-in-the-pathogenesis-of-alzheimer-disease-and-other-selected-age-related-neurodegenerative-disorders
#14
Fabio Di Domenico, Antonella Tramutola, D Allan Butterfield
Oxidative stress is involved in various and numerous pathological states including several age-related neurodegenerative diseases. Peroxidation of the membrane lipid bilayer is one of the major sources of free radical-mediated injury that directly damages neurons causing increased membrane rigidity, decreased activity of membrane-bound enzymes, impairment of membrane receptors and altered membrane permeability and eventual cell death. Moreover, the peroxidation of polyunsaturated fatty acids leads to the formation of aldehydes, which can act as toxic by-products...
October 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27780330/enhancing-approaches-to-the-identification-and-management-of-pseudobulbar-affect
#15
David W Crumpacker
Pseudobulbar affect (PBA) is a socially debilitating condition that primarily affects people with neurologic diseases, such as Alzheimer's disease or multiple sclerosis. This condition is characterized by uncontrolled, exaggerated expressions of laughing or crying-often when the situation does not warrant this behavior. Although the true prevalence of PBA is surprisingly high, this condition remains widely misdiagnosed and underdiagnosed. While its exact etiology is unknown, PBA likely results from disruptions in the brain structures and/or neurotransmitters that regulate emotions...
September 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27776428/coriandrum-sativum-suppresses-a%C3%AE-42-induced-ros-increases-glial-cell-proliferation-and-erk-activation
#16
Quan Feng Liu, Haemin Jeong, Jang Ho Lee, Yoon Ki Hong, Youngje Oh, Young-Mi Kim, Yoon Seok Suh, Semin Bang, Hye Sup Yun, Kyungho Lee, Sung Man Cho, Sung Bae Lee, Songhee Jeon, Young-Won Chin, Byung-Soo Koo, Kyoung Sang Cho
Alzheimer's disease (AD), the most common neurodegenerative disease, has a complex and widespread pathology that is characterized by the accumulation of amyloid [Formula: see text]-peptide (A[Formula: see text]) in the brain and various cellular abnormalities, including increased oxidative damage, an amplified inflammatory response, and altered mitogen-activated protein kinase signaling. Based on the complex etiology of AD, traditional medicinal plants with multiple effective components are alternative treatments for patients with AD...
October 25, 2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27771474/sex-differences-in-the-prevalence-and-incidence-of-mild-cognitive-impairment-a-meta-analysis
#17
Bonnie Au, Sydney Dale-McGrath, Mary C Tierney
OBJECTIVE: More women have Alzheimer's disease (AD) than men. Understanding sex differences in mild cognitive impairment (MCI) may further knowledge of AD etiology and prevention. We conducted a meta-analysis to examine sex differences in the prevalence and incidence of MCI, which included amnestic and non-amnestic subtypes. METHOD: Systematic searches were performed in July 2015 using MEDLINE/PubMed, Scopus, and PsycINFO for population-or community-based studies with MCI data for men and women...
October 19, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27767994/cholinergic-basal-forebrain-lesion-decreases-neurotrophin-signaling-without-affecting-tau-hyperphosphorylation-in-genetically-susceptible-mice
#18
Marion T Turnbull, Elizabeth J Coulson
Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation...
October 20, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27767990/the-proactive-self-in-space-how%C3%A2-egocentric-and-allocentric-spatial-impairments-contribute-to-anosognosia-in%C3%A2-alzheimer-s-disease
#19
Silvia Serino, Giuseppe Riva
In addition to impairments in episodic and spatial memory, anosognosia (i.e., loss of awareness of the deficient aspect of own cognitive functioning) may be considered an important cognitive marker of Alzheimer's disease (AD). However, although a growing body of interesting models have been proposed to explain this early symptom, what is still missing is a unifying framework of all the characteristic signs occurring in patients with AD that may guide the search for its causal neuropathological process and, ultimately, the etiological process...
October 20, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27761111/sexual-dimorphism-and-aging-in-the-human-hyppocampus-identification-validation-and-impact-of-differentially-expressed-genes-by-factorial-microarray-and-network-analysis
#20
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
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