scholarly journals How to do things with (thousands of) words: Computational approaches to discourse analysis in Alzheimer's disease

Cortex ◽  
2020 ◽  
Vol 129 ◽  
pp. 446-463
Author(s):  
Natasha Clarke ◽  
Peter Foltz ◽  
Peter Garrard
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Discourse Analysis ◽  
Computational Approaches

scholarly journals High-throughput screening of natural compounds and inhibition of a major therapeutic target HsGSK-3β for Alzheimer’s disease using computational approaches

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rohit Shukla ◽  
Tiratha Raj Singh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Throughput Screening ◽  
Complex Disease ◽  
Glycogen Synthase ◽  
Binding Free Energy ◽  
Drug Candidate ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Computational Approaches

Abstract Background Alzheimer’s disease is a leading neurodegenerative disease worldwide and is the 6th leading cause of death in the USA. AD is a very complex disease and the drugs available in the market cannot fully cure it. The glycogen synthase kinase 3 beta plays a major role in the hyperphosphorylation of tau protein which forms the neurofibrillary tangles which is a major hallmark of AD. In this study, we have used a series of computational approaches to find novel inhibitors against GSK-3β to reduce the TAU hyperphosphorylation. Results We have retrieved a set of compounds (n=167,741) and screened against GSK-3β in four sequential steps. The resulting analysis of virtual screening suggested that 404 compounds show good binding affinity and can be employed for pharmacokinetic analysis. From here, we have selected 20 compounds those were good in terms of pharmacokinetic parameters. All these compounds were re-docked by using Autodock Vina followed by Autodock. Four best compounds were employed for MDS and here predicted RMSD, RMSF, Rg, hydrogen bonds, SASA, PCA, and binding-free energy. From all these analyses, we have concluded that out of 167,741 compounds, the ZINC15968620, ZINC15968622, and ZINC70707119 can act as lead compounds against HsGSK-3β to reduce the hyperphosphorylation. Conclusion The study suggested three compounds (ZINC15968620, ZINC15968622, and ZINC70707119) have great potential to be a drug candidate and can be tested using in vitro and in vivo experiments for further characterization and applications.

P2-082: Discourse analysis of Alzheimer's disease patients: From the lexicon to discourse

2010 ◽  
Vol 6 ◽  
pp. S337-S337
Author(s):  
Renne P. Alegria ◽  
Ricardo B. Ferreira ◽  
Rita C.G. Marques ◽  
Cassio M.C. Bottino ◽  
Maria I. Nogueira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Discourse Analysis

Connected Speech Deficit as an Early Hallmark of CSF-defined Alzheimer’s Disease and Correlation with Cerebral Hypoperfusion Pattern

2019 ◽  
Vol 16 (6) ◽  
pp. 483-494 ◽  
Author(s):  
Giulia Mazzon ◽  
Miloš Ajčević ◽  
Tatiana Cattaruzza ◽  
Alina Menichelli ◽  
Michele Guerriero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Discourse Analysis ◽  
Language Processing ◽  
Anterior Part ◽  
Inferior Frontal Gyrus ◽  
Cerebral Hypoperfusion ◽  
Global Coherence ◽  
Prodromal Alzheimer’S Disease ◽  
Mci Due To Ad

Background: Diagnosis of prodromal Alzheimer's disease (AD) still represents a hot topic and there is a growing interest for the detection of early and non-invasive biomarkers. Although progressive episodic memory impairment is the typical predominant feature of AD, communicative difficulties can be already present at the early stages of the disease. Objective: This study investigated the narrative discourse production deficit as a hallmark of CSFdefined prodromal AD and its correlation with cerebral hypoperfusion pattern. Method: Narrative assessment with a multilevel procedure for discourse analysis was conducted on 28 subjects with Mild Cognitive Impairment (15 MCI due to AD; 13 MCI non-AD) and 28 healthy controls. The diagnostic workup included CSF AD biomarkers. Cerebral hypoperfusion pattern was identified by SPECT image processing. Results: The results showed that the discourse analysis of global coherence and lexical informativeness indexes allowed to identify MCI due to AD from MCI non-AD and healthy subjects. These findings allow to hypothesize that the loss of narrative efficacy could be a possible early clinical hallmark of Alzheimer’s disease. Furthermore, a significant correlation of global coherence and lexical informativeness reduction with the SPECT hypoperfusion was found in the dorsal aspect of the anterior part of the left inferior frontal gyrus, supporting the hypothesis that this area has a significant role in communicative efficacy, and in particular, in semantic selection executive control. Conclusion: This study contributes to the understanding of the neural networks for language processing and their involvement in prodromal Alzheimer's disease. It also suggests an easy and sensitive tool for clinical practice that can help identifying individuals with prodromal Alzheimer’s disease.

scholarly journals Near-atomic model of microtubule-tau interactions

Science ◽  
2018 ◽  
Vol 360 (6394) ◽  
pp. 1242-1246 ◽  
Author(s):  
Elizabeth H. Kellogg ◽  
Nisreen M. A. Hejab ◽  
Simon Poepsel ◽  
Kenneth H. Downing ◽  
Frank DiMaio ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Atomic Model ◽  
Developmentally Regulated ◽  
Computational Approaches ◽  
Atomic Models ◽  
Cryo Electron Microscopy ◽  
Tubulin Binding ◽  
Axonal Protein

Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer’s disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo–electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces.

Interactional differences in Alzheimer's discourse: An examination of AD speech across two audiences

1994 ◽  
Vol 23 (1) ◽  
pp. 31-58 ◽  
Author(s):  
Vai Ramanathan-Abbott
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Discourse Analysis ◽  
Social Interaction ◽  
The Other ◽  
Psycholinguistic Research ◽  
Narrative Skills ◽  
Narrative Abilities

ABSTRACTAssessments of the narrative abilities of patients suffering from Alzheimer's disease should consider the interactions that generate the narratives. By analyzing the discourse of an AD patient in interaction with two different interlocutors, namely her husband and the author, this study calls attention to ways in which one interaction facilitates narratives and the other does not. Previous psycholinguistic research, largely focusing on the resultant narrative, has understood the AD patient's deteriorating narrative skills as a result of the progressively debilitating nature of the disease. This is undoubtedly true, but extensive and meaningful talk is nevertheless possible, partially grounded in and constructed through social interaction. (Discourse analysis, Alzheimer's disease, narrative social interaction)

Cognitive control constrains memory attributions

2019 ◽  
Vol 42 ◽  
Author(s):  
Colleen M. Kelley ◽  
Larry L. Jacoby
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Control

Abstract Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.

Formation of paired helical filaments in Alzheimer's disease

1984 ◽  
Vol 42 ◽  
pp. 302-303
Author(s):  
J. Metuzals ◽  
D. F. Clapin ◽  
V. Montpetit
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Lobe ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Normal Brain ◽  
Protein Assemblies ◽  
Electron Microscopic ◽  
Helical Symmetry ◽  
Structural Levels

Information on the conformation of paired helical filaments (PHF) and the neurofilamentous (NF) network is essential for an understanding of the mechanisms involved in the formation of the primary lesions of Alzheimer's disease (AD): tangles and plaques. The structural and chemical relationships between the NF and the PHF have to be clarified in order to discover the etiological factors of this disease. We are investigating by stereo electron microscopic and biochemical techniques frontal lobe biopsies from patients with AD and squid giant axon preparations. The helical nature of the lesion in AD is related to pathological alterations of basic properties of the nervous system due to the helical symmetry that exists at all hierarchic structural levels in the normal brain. Because of this helical symmetry of NF protein assemblies and PHF, the employment of structure reconstruction techniques to determine the conformation, particularly the handedness of these structures, is most promising. Figs. 1-3 are frontal lobe biopsies.

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