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Integrative Network-Based Analysis Reveals Gene Networks and Novel Drug Repositioning Candidates for Alzheimer Disease

Zachary F. Gerring, Eric R. Gamazon, Anthony White, Eske M. Derks
2021 Neurology: Genetics  
for Alzheimer disease.MethodsWe integrated genome-wide association summary statistics for Alzheimer disease with tissue-specific gene coexpression networks from brain tissue samples in the Genotype-Tissue  ...  are enriched in brain gene coexpression networks involved in the immune response.  ...  IGAP was made possible by the generous participation of the controls, the patients, and their families.  ... 
doi:10.1212/nxg.0000000000000622 pmid:34532569 pmcid:PMC8441674 fatcat:l6ifkgwx7rapzdd6milkcrek6e

Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders

Neelroop N. Parikshak, Michael J. Gandal, Daniel H. Geschwind
2015 Nature reviews genetics  
Acknowledgements The authors thank L. de la Torre-Ubieta and H. Won for assistance with Figure 1 , as well as members of the Geschwind laboratory and K. Lage for critical reading of the manuscript.  ...  Given that the human brain transcriptome has a reproducible structure 12, 26 , one useful way to explore how mutations in risk genes perturb typical brain development is to map risk genes onto transcriptional  ...  Inter-modular connectivity reflects a higher-order structure of biological relationships in a gene network, and intra-modular connectivity can identify which genes are biological hubs within modules.  ... 
doi:10.1038/nrg3934 pmid:26149713 pmcid:PMC4699316 fatcat:nbpdeq7rgzdszmlyrnmunduexy

Genetic variants in Alzheimer disease — molecular and brain network approaches

Chris Gaiteri, Sara Mostafavi, Christopher J. Honey, Philip L. De Jager, David A. Bennett
2016 Nature Reviews Neurology  
In this review, we discuss how the study of molecular, cellular and brain networks provides additional information on the effect of LOAD-associated genetic variants.  ...  Further, we highlight the clinical potential of mechanistically coupling genetic variants and disease phenotypes with multiscale brain models.  ...  The phenotypic effects of Alzheimer disease (AD)-associated genetic variants are exerted through several types of molecular networks (here extracted from GeneMANIA), or even alter their structure.  ... 
doi:10.1038/nrneurol.2016.84 pmid:27282653 pmcid:PMC5017598 fatcat:yjgh3kc3tvhqfdc4r32nfyopwy

Complexity across scales: a walkthrough to linking neuro-imaging readouts to molecular processes

Anandhi Iyappan, Sepehr Golriz Khatami, Martin Hofmann-Apitius
2017 Journal of Systems and Integrative Neuroscience  
They help in measuring the structure of white matter as well as fiber connectivity within and across brain regions [36][37][38]. Fractional anisotropy is a numerical measure of fiber integrity.  ...  The latest MRI techniques still are not capable of examining individual layers of the cortex.  ...  Structural MRI is widely used to examine the shape, size and structural alterations in the brain regions [20, 21] .  ... 
doi:10.15761/jsin.1000151 fatcat:oomqcbhhrbgfjaobbrvn25lcnq

Genetics of Alzheimer´S Disease [chapter]

Victoria Campos-Pea, Roco Gmez, Marco Antonio
2014 Neurochemistry  
Late onset alzheimer´s disease Apoe risk gene Allele 4 of apolipoprotein E (ApoE4) has been reported to represent the main identified risk factor for sporadic AD [44, 49, 108] .  ...  Under normal conditions, Tau is a highly soluble protein, since it contains no apparent secondary structure [33] [34] .  ... 
doi:10.5772/58286 fatcat:srkmr5srwfaqzpk7sntbhvtv6u

Risk Variants in Three Alzheimer's Disease Genes Show Association with EEG Endophenotypes

Ana Macedo, Carlos Gómez, Miguel Ângelo Rebelo, Jesús Poza, Iva Gomes, Sandra Martins, Aarón Maturana-Candelas, Víctor Gutiérrez-de Pablo, Luis Durães, Patrícia Sousa, Manuel Figueruelo, Maria Rodriguez (+6 others)
2021 Journal of Alzheimer's Disease  
The slowing of brain activity was observed in carriers of risk alleles in IL1RAP (rs10212109, rs9823517, rs4687150), UNC5C (rs17024131), and NAV2 (rs1425227, rs862785) genes, regardless of the disease  ...  At the clinical level, one of the most common physiological alterations is the slowing of oscillatory brain activity, measurable by electroencephalography (EEG).  ...  The inclusion of these genes in our analysis could improve the knowledge of their role in brain physiology.The set of sixteen selected candidate genes and ).  ... 
doi:10.3233/jad-200963 pmid:33522999 pmcid:PMC8075394 fatcat:wy6zh5voufhuflbfhb7fwjqtli

Recent Alzheimer's disease research highlights

Douglas Galasko, Todd Golde, Gordon Wilcock
2012 Alzheimer's Research & Therapy  
Th e second included neuronally diff erentiated iPS cells from reprogrammed fi broblasts of two APP gene duplication carriers, two patients with sporadic AD and two controls [2].  ...  Th ough the consistency of the fi ndings across the three studies is reassuring, they still only report on the phenotypes of a handful of cell lines from those at risk for AD.  ...  that leads to neurodegeneration and irreversible structural changes in the brain [14] [15] [16] [17] .  ... 
doi:10.1186/alzrt117 pmid:22594696 pmcid:PMC3506929 fatcat:kxdtsma3vvhxld7hgxgxvmvbcq

Clinical Study of Memory Disorders in Aging Patients and Associated Pathology

Castejón OJ, Carrero Gonzalez CM, Lastre G, Galindez P, Salones de Castejón M, Sierra Carrero L
2021 Journal of Clinical and Biomedical Investigation  
pathology (21%), such as constipation, loss of sphincter control, and gastritis, arthritis (13%), prostatic hypertrophy (1%) and loss of weight (1%).  ...  language (36%), neurosensory disorders (28%), as diminution of visual and hearing acuity, dizziness (26%), Parkinson disease (34%), Alzheimer disease (21%), gait disturbances (10%), vertigo (10%), cervicalgia  ...  One of the features of Parkinson Disease (PD) is the alteration of voice and speech.  ... 
doi:10.52916/jcbi214004 fatcat:qx5hpq4havhbrntbxpk6vehqzu

The genetics of mental illness: implications for practice

S E Hyman
2000 Bulletin of the World Health Organization  
Knowledge of the timing of the expression of risk genes during brain development and of their function should not only contribute to an understanding of gene action and the pathophysiology of disease but  ...  The concept of the causative gene has been replaced by that of genetic complexity, in which multiple genes act in concert with non-genetic factors to produce a risk of mental disorder.  ...  Acknowledgements The author thanks Paul Sirovatka, Steven Moldin and Hemin Chin for invaluable help with the manuscript. Ré sumé Gé né tique et maladie mentale : incidences sur la pratique  ... 
pmid:10885164 pmcid:PMC2560734 fatcat:vzadjjjdancrvjvyyxxeedypvu

Genetic and Degenerative Neurological Disorders ? an Emphasis on Alzheimer?s, the Mystery

Hima Bindu A, Aliya Siddiqui
2011 Journal of genetic syndrome & gene therapy  
Neurologic diseases are disorders of the brain, spinal cord and nerves throughout the body.  ...  AD involves an economical and emotional cost; hence the understanding of aspects related with AD prevalence, risk factors and potential interventions are topics of significant importance for medical attention  ...  Most of the antioxidants measured were lower in the AD patients compared to the controls [53] . There are strong connections among mitochondria, aging, and Alzheimer's disease (AD) [54] .  ... 
doi:10.4172/2157-7412.1000109 fatcat:3wdbx72hwfc6jjbn4ufyuayoce

Do Microglia Default on Network Maintenance in Alzheimer's Disease?

Katherine A. Southam, Adele J. Vincent, David H. Small
2016 Journal of Alzheimer's Disease  
Genome-wide association studies have identified a wide array of risk-associated genes for AD, many of which are associated with abnormal functioning of immune cells.  ...  Although the cause of Alzheimer's disease (AD) remains unknown, a number of new findings suggest that the immune system may play a critical role in the early stages of the disease.  ...  KAS is the recipient of a part-funded fellowship from the Alzheimer's Australia Dementia Research Foundation (AADRF).  ... 
doi:10.3233/jad-151075 pmid:26890782 pmcid:PMC4927862 fatcat:4qmgv7ahlnf7zaxsymbcw5yype

Neurophysiology of Social Conduct and Impact of Adverse Exposures

Abhay Kumar Pandey, Bajarangprasad L. Pandey
2016 Avicenna Journal of Neuro Psycho Physiology  
Description of neuroanatomical projection paths in the brain white matter and acceptance of "associationistic" models of cognitive function helped develop the concept of network in neurology (2).  ...  Human social conduct draws upon focal as well as global connected brain mechanisms. These flexible anatomical routes operate in cooperation and coordination for intelligent behaviors.  ...  Information in the brain is stored in form of altered structure and chemistry of synapses involving continuous making and unmaking of synapses (1) .  ... 
doi:10.5812/ajnpp.12452 fatcat:huceo63gyzg25pi6o6xeuvldfm

Risk Factors for Alzheimer's Disease [chapter]

Dongming Cai, Farida El Gaamouch
2016 Update on Dementia  
Several findings suggest that multiple risk genes and factors may contribute to the pathogenesis of LOAD.  ...  Approximately 50% of the FAD patients carry mutations in one of the following genes: APP, PSEN1, and PSEN2.  ...  Acknowledgements This work was supported in whole or in part by funding from Alzheimer Association (NIRP14-304720), Department of Veteran Affairs RR&D SPiRE (1I21RX001558-01A1), and NIH R01 (1R01AG048923  ... 
doi:10.5772/64270 fatcat:kkafvscucfbnlavkmrnab4hlbu

Pathobiolgy and Management of Alzheimer's Disease

Hoowon Kim, Ji Yeon Chung
2021 Chonnam medical journal  
Future development of preventive and therapeutic modalities may be dependent on the pathobiology of Alzheimer's disease.  ...  Environmental factors such as bacterial and viral infections, heavy metal ions, diet, sleep, stress, and gut microbiota are also risk factors of Alzheimer's disease.  ...  [48] [49] [50] In addition, recent genetic studies including genome-wide association studies (GWAS) have identified about 20 well-validated genes harboring risk alleles, of which about half are predominantly  ... 
doi:10.4068/cmj.2021.57.2.108 pmid:34123738 pmcid:PMC8167446 fatcat:tmmjmurdvjdjvftoi47o2q37sm

The unsolved relationship of brain aging and late-onset Alzheimer disease

Andreas Kern, Christian Behl
2009 Biochimica et Biophysica Acta - General Subjects  
This review focuses on structural and functional alterations of the brain during aging, age-associated imbalances of defences against oxidative stress and age-related alterations of the metabolism of Aβ  ...  Although our understanding of brain region-specific neuronal aging is still incomplete, the early structural and molecular changes in the transition from cognitive health to impairment are subtle and the  ...  The research projects of the Behl-Lab on Alzheimer disease are funded in part by the Gottschalk Stiftung.  ... 
doi:10.1016/j.bbagen.2009.07.016 pmid:19632303 fatcat:ckw66jja7nffjbezb2pomgzf3i
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