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Alzheimer's etiologies

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https://www.readbyqxmd.com/read/29768996/a-systematic-review-on-donepezil-based-derivatives-as-potential-cholinesterase-inhibitors-for-alzheimer-s-disease
#1
Jan Korabecny, Katarina Spilovska, Eva Mezeiova, Ondrej Benek, Radomir Juza, Daniel Kaping, Ondrej Soukup
Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine...
May 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29766738/the-role-of-gene-editing-in-neurodegenerative-diseases
#2
Hueng-Chuen Fan, Ching-Shiang Chi, Yih-Jing Lee, Jeng-Dau Tsai, Shinn-Zong Lin, Horng-Jyh Harn
Neurodegenerative diseases (NDs), at least including Alzheimer's, Huntington's, and Parkinson's diseases, have become the most dreaded maladies because there are no precise diagnostic tools or definite treatments for these debilitating diseases. The increased prevalence and a substantial impact on the social-economic and medical care of NDs propel governments to develop policies to counteract the impact. Although the etiologies of NDs are still unknown, growing evidence suggests that genetic, cellular, and circuit alternations may cause the generation of abnormal misfolded proteins, which uncontrolledly accumulate to damage and eventually overwhelm the protein-disposal mechanisms of these neurons, leading to a common pathological feature of NDs...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29740579/the-role-of-genetics-in-advancing-precision-medicine-for-alzheimer-s-disease-a-narrative-review
#3
REVIEW
Yun Freudenberg-Hua, Wentian Li, Peter Davies
Alzheimer's disease (AD) is the most common type of dementia, which has a substantial genetic component. AD affects predominantly older people. Accordingly, the prevalence of dementia has been rising as the population ages. To date, there are no effective interventions that can cure or halt the progression of AD. The only available treatments are the management of certain symptoms and consequences of dementia. The current state-of-the-art medical care for AD comprises three simple principles: prevent the preventable, achieve early diagnosis, and manage the manageable symptoms...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29734664/blood-ammonia-as-a-possible-etiological-agent-for-alzheimer-s-disease
#4
REVIEW
Yan Yan Jin, Parul Singh, Hea-Jong Chung, Seong-Tschool Hong
Alzheimer’s disease (AD), characterized by cognitive decline and devastating neurodegeneration, is the most common age-related dementia. Since AD is a typical example of a complex disease that is affected by various genetic and environmental factors, various factors could be involved in preventing and/or treating AD. Extracellular accumulation of beta-amyloid peptide (Aβ) and intracellular accumulation of tau undeniably play essential roles in the etiology of AD. However, interestingly enough, medications targeting Aβ or tau all failed and the only clinically efficient medications for AD are drugs targeting the cholinergic pathway...
May 4, 2018: Nutrients
https://www.readbyqxmd.com/read/29726758/pharmacotherapy-for-the-treatment-of-depression-in-patients-with-alzheimer-s-disease-a-treatment-resistant-depressive-disorder
#5
Madia Lozupone, Maddalena La Montagna, Francesca D'Urso, Carla Piccininni, Rodolfo Sardone, Vittorio Dibello, Gianluigi Giannelli, Vincenzo Solfrizzi, Antonio Greco, Antonio Daniele, Nicola Quaranta, Davide Seripa, Antonello Bellomo, Giancarlo Logroscino, Francesco Panza
Pharmacotherapy for the treatment of depressive disorders in Alzheimer's Disease (AD) represents a clinical challenge. pharmacological options are often attempted after a period of watchful waiting (8-12 weeks). monoaminergic antidepressant drugs have shown only modest or null clinical benefits, maybe because the etiology of depressive symptoms in ad patients is fundamentally different from that of nondemented subjects. Areas covered: The following article looks at the selective serotonin reuptake inhibitor sertraline, which is one of the most frequently studied antidepressant medications in randomized controlled trials (RCTs)...
May 4, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29724603/high-prevalence-of-olfactory-dysfunction-in-cervical-dystonia
#6
Milena Marek, Susanne Linnepe, Christine Klein, Thomas Hummel, Sebastian Paus
INTRODUCTION: Olfactory dysfunction has been established as a frequent non-motor symptom in neurodegenerative and movement disorders such as Parkinson's disease, Alzheimer's disease, and hereditary ataxias. To expand knowledge of non-motor symptoms in dystonia, and to test for a potential endophenotype, we examined olfactory function in cervical dystonia (CD). METHODS: In patients with CD, and neurologically healthy controls, olfactory function was examined by "Sniffin' Sticks", a test of nasal chemosensory function based on pen-like odor dispensing devices...
April 25, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29723294/probing-the-role-of-ppar%C3%AE-in-the-regulation-of-late-onset-alzheimer-s-disease-associated-genes
#7
Julio Barrera, Shobana Subramanian, Ornit Chiba-Falek
Peroxisome proliferator-activated receptor-γ (PPARγ), is a transcription factor that governs pathways, such as lipid metabolism and immune response, that have been implicated in the etiology of LOAD. Previously, we established HepG2-derived cell-lines with stable knockdown of PPARγ gene, and showed an increase in mRNA levels of genes mapped in the APOE linkage disequilibrium (LD) region on chromosome 19q13.32, with the greatest effect observed for APOE-mRNA. Here, we extended the analysis using our PPARγ knockdown model system and investigated the broader effect on expression changes of genes implicated in LOAD via genome wide association studies (GWAS)...
2018: PloS One
https://www.readbyqxmd.com/read/29720226/increased-a20-e3-ubiquitin-ligase-interactions-in-bid-deficient-glia-attenuate-tlr3-and-tlr4-induced-inflammation
#8
Sinéad Kinsella, Michael Fichtner, Orla Watters, Hans-Georg König, Jochen H M Prehn
BACKGROUND: Chronic pro-inflammatory signaling propagates damage to neural tissue and affects the rate of disease progression. Increased activation of Toll-like receptors (TLRs), master regulators of the innate immune response, is implicated in the etiology of several neuropathologies including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. Previously, we identified that the Bcl-2 family protein BH3-interacting domain death agonist (Bid) potentiates the TLR4-NF-κB pro-inflammatory response in glia, and specifically characterized an interaction between Bid and TNF receptor associated factor 6 (TRAF6) in microglia in response to TLR4 activation...
May 2, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29717631/hypoxia-and-reactive-oxygen-species-as-modulators-of-endoplasmic-reticulum-and-golgi-homeostasis
#9
Daniela Mennerich, Sakari Kellokumpu, Thomas Kietzmann
SIGNIFICANCE: Eukaryotic cells execute various functions in subcellular compartments or organelles for which cellular redox homeostasis is of importance. Apart from mitochondria, hypoxia and stress mediated formation of reactive oxygen species (ROS) were shown to modulate endoplasmic reticulum (ER) and Golgi apparatus (GA) functions. Recent Advances: Research during the last decade has improved our understanding of disulfide bond formation, protein glycosylation and secretion as well as pH and redox homeostasis in the endoplasmic reticulum (ER) and Golgi apparatus (GA)...
May 2, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29714994/issues-in-geriatric-care-alzheimer-disease
#10
Kathy Kemle, Richard J Ackermann
Alzheimer disease (AD) occurs in 8.8% of older US adults and is the sixth leading cause of death among older adults. Medicare annual wellness visits require screening for cognitive impairment but do not specify screening methods. Numerous screening instruments are available. If results are positive, evaluation with well-validated assessment tools is needed. If cognitive impairment is confirmed, laboratory tests and imaging studies should be obtained to rule out reversible etiologies. If patients meet diagnostic criteria for AD, clinicians should educate patients and families on the expected course and help them complete advance directives...
May 2018: FP Essentials
https://www.readbyqxmd.com/read/29710711/frequency-and-correlates-of-subjective-memory-complaints-in-parkinson-s-disease-with-and-without-mild-cognitive-impairment-data-from-the-parkinson-s-disease-cognitive-impairment-study
#11
Roberta Baschi, Alessandra Nicoletti, Vincenzo Restivo, Deborah Recca, Mario Zappia, Roberto Monastero
Subjective memory complaints (SMC) may represent the preclinical phase of mild cognitive impairment (MCI) due to Alzheimer's disease. Dementia/MCI have been described with a high prevalence in Parkinson's disease (PD), but whether SMC may predict the development of cognitive impairment has been barely explored. To evaluate the frequency and clinical correlates of isolated SMC (PD-SMC) or within the construct of MCI in subjects with PD, 147 PD patients from the PArkinson's disease COgnitive impairment Study (PACOS) were consecutively recruited for the study...
April 25, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29707086/epigenetics-of-metabolic-syndrome-as-a-mood-disorder
#12
REVIEW
Sermin Kesebir
Mood disorders comprise major depressive disorder (MDD), bipolar disorder (BD) and the milder forms of these two disorders. Reccurring MDD is also known as unipolar disorder. The distinction between unipolar and bipolar disorders was first suggested in 1957 by Leonard and was made official after support by several studies in 1980. Indeed, in 150 AD, Aretaeus of Cappadocia wrote "It seems to me that melancholia is the beginning and a part of mania". Additionally, Kraepelin, who proposed the first medical disease model in psychiatry a century ago, considered recurrent unipolar depression cases under the category of bipolar disorder and conceptualized spectrum disorders...
June 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29706957/microglia-and-beyond-innate-immune-cells-as-regulators-of-brain-development-and-behavioral-function
#13
REVIEW
Kathryn M Lenz, Lars H Nelson
Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29703947/human-brain-arousal-in-the-resting-state-a-genome-wide-association-study
#14
Philippe Jawinski, Holger Kirsten, Christian Sander, Janek Spada, Christine Ulke, Jue Huang, Ralph Burkhardt, Markus Scholz, Tilman Hensch, Ulrich Hegerl
Arousal affects cognition, emotion, and behavior and has been implicated in the etiology of psychiatric disorders. Although environmental conditions substantially contribute to the level of arousal, stable interindividual characteristics are well-established and a genetic basis has been suggested. Here we investigated the molecular genetics of brain arousal in the resting state by conducting a genome-wide association study (GWAS). We selected N = 1877 participants from the population-based LIFE-Adult cohort...
April 27, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29702072/structure-of-app-c99-1-99-and-implications-for-role-of-extra-membrane-domains-in-function-and-oligomerization
#15
George A Pantelopulos, John E Straub, D Thirumalai, Yuji Sugita
The 99 amino acid C-terminal fragment of Amyloid Precursor Protein APP-C99 (C99) is cleaved by γ-secretase to form Aβ peptide, which plays a critical role in the etiology of Alzheimer's Disease (AD). The structure of C99 consists of a single transmembrane domain flanked by intra and intercellular domains. While the structure of the transmembrane domain has been well characterized, little is known about the structure of the flanking domains and their role in C99 processing by γ-secretase. To gain insight into the structure of full-length C99, REMD simulations were performed for monomeric C99 in model membranes of varying thickness...
April 24, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29692948/varifunnet-an-integrated-multiscale-modeling-framework-to-study-the-effects-of-rare-non-coding-variants-in-genome-wide-association-studies-applied-to-alzheimer-s-disease
#16
Qiao Liu, Chen Chen, Annie Gao, Hang Hang Tong, Lei Xie
It is a grand challenge to reveal the causal effects of DNA variants in complex phenotypes. Although statistical techniques can establish correlations between genotypes and phenotypes in Genome-Wide Association Studies (GWAS), they often fail when the variant is rare. The emerging Network-based Association Studies aim to address this shortcoming in statistical analysis, but are mainly applied to coding variations. Increasing evidences suggest that non-coding variants play critical roles in the etiology of complex diseases...
November 2017: Proceedings
https://www.readbyqxmd.com/read/29687167/bri2-as-an-anti-alzheimer-gene
#17
REVIEW
Shuji Matsuda, Takao Senda
There are several theories regarding the etiologies of Alzheimer disease (AD). Considering that all genes responsible for familial AD are amyloid protein precursor (APP) or APP metabolizing enzymes, surely aberrant APP metabolism is crucial to pathogenesis of AD. BRI2, a type II transmembrane protein, binds APP and inhibits all α, β, and γ pathways of APP proteolysis. Crossing AD model mice with BRI2 transgenic or BRI2 knockout mice confirmed that BRI2 is an anti-Alzheimer gene. Mutations of BRI2 are known to cause rare familial dementias in human...
April 23, 2018: Medical Molecular Morphology
https://www.readbyqxmd.com/read/29683094/role-of-inflammatory-markers-in-elderly-type-2-diabetic-patients-with-mild-cognitive-impairment
#18
Salwa S Hosny, Ahmed M Bahaaeldin, Mohamed S Khater, Meram M Bekhet, Hayam A Hebah, Ghada A Hasanin
BACKGROUND: Type 2 diabetes (T2DM) is a risk factor for Alzheimer's disease and mild cognitive impairment. The etiology of cognitive impairment in people with T2DM is uncertain but, chronic hyperglycemia, cerebral micro vascular disease, severe hypoglycemia, and increased prevalence of macro vascular disease are implicated. OBJECTIVES: to determine the serum levels of soluble vascular adhesion molecule (sVCAM-1) and highly sensitive C-reactive protein (hs-CRP) in elderly type 2 diabetics with mild cognitive impairment (MCI)...
April 22, 2018: Current Diabetes Reviews
https://www.readbyqxmd.com/read/29678670/etiology-of-type-2-diabetes-and-alzheimer-s-disease-exploring-the-mitochondria
#19
REVIEW
Talisa K Silzer, Nicole R Phillips
Type 2 diabetes is a significant risk factor for developing Alzheimer's disease later in life, and particular populations have a disproportionate risk because of the high prevalence of type 2 diabetes. There are many overlapping pathologies, and teasing out the primary root cause, if one indeed exists, is very difficult. Here, we review (1) the key facets of mitochondrial biology that are relevant to the two conditions, and (2) the role that mitochondrial dysfunction plays in the shared pathophysiology. We posit that mitochondrial dysfunction lies at the root of the affected processes rather than alongside them as a co-pathology...
April 17, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29676229/viral-induced-oxidative-and-inflammatory-response-in-alzheimer-s-disease-pathogenesis-with-identification-of-potential-drug-candidates-a-systematic-review-using-systems-biology-approach
#20
Puneet Talwar, Renu Gupta, Suman Kushwaha, Rachna Agarwal, Luciano Saso, Shrikant Kukreti, Ritushree Kukreti
Alzheimer's disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets...
April 19, 2018: Current Neuropharmacology
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