COMPASS: A computational model to predict changes in MMSE scores 24-months after initial assessment of Alzheimer’s disease

AbstractThe longitudinal assessment of episodic and semantic memory was obtained from 236 patients diagnosed with Alzheimer’s disease (AD, n = 128) and with frontotemporal lobar degeneration (FTLD, n = 108), including patients with a social comportment/dysexecutive (SOC/EXEC) disorder, progressive nonfluent aphasia (PNFA), semantic dementia (SemD), and corticobasal syndrome (CBS). At the initial assessment, AD patients obtained a lower score on the delayed free recall test than other patients. Longitudinal analyses for delayed free recall found converging performance, with all patients reaching the same level of impairment as AD patients. On the initial evaluation for delayed recognition, AD patients also obtained lower scores than other groups. Longitudinal analyses for delayed recognition test performance found that AD patients consistently produced lower scores than other groups and no convergence between AD and other dementia groups was seen. For semantic memory, there were no initial between-group differences. However, longitudinal analyses for semantic memory revealed group differences over illness duration, with worse performance for SemD versus AD, PNFA, SOC/EXEC, and CBS patients. These data suggest the presence of specific longitudinal patterns of impairment for episodic and semantic memory in AD and FTLD patients suggesting that all forms of dementia do not necessarily converge into a single phenotype. (JINS, 2010, 16, 278–286.)

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Increased Platelet Membrane Fluidity in Alzheimer’s Disease: An Initial Assessment of Specificity

Neuropsychopharmacology ◽

10.1007/978-3-642-74034-3_14 ◽

1990 ◽

pp. 142-147 ◽

Cited By ~ 1

Author(s):

G. S. Zubenko

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Membrane Fluidity ◽

Platelet Membrane ◽

Initial Assessment

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Simulation of Ca2+ oscillations in astrocytes mediated by amyloid beta in Alzheimer’s disease

10.1101/2020.03.18.996843 ◽

2020 ◽

Author(s):

Huayi Gao ◽

Langzhou Liu ◽

Shangbin Chen

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Computational Model ◽

Glutamate Receptors ◽

Amyloid Beta ◽

Amyloid Beta Peptide ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Beta Peptide ◽

Intracellular Ca

AbstractDisruptions of astrocyte Ca2+ signaling is important in Alzheimer’s disease (AD) with the unclear mechanism of amyloid beta peptide (Aβ). We have modified our previous computational model of spontaneous Ca2+ oscillations in astrocytes to investigate the effects of Aβ on intracellular Ca2+ dynamics. The simulation results have shown consistence with the previous experiments. Aβ can increase the resting concentration of intracellular Ca2+ and change the regime of Ca2+ oscillations by activating L-type voltage-gated calcium channels and the metabolic glutamate receptors, or by increasing ryanodine receptors sensitivity and Ca2+ leakage, respectively. This work have provided a toolkit to study the influence of Aβ on intracellular Ca2+ dynamics in AD. It is helpful for understanding the toxic role of Aβ during the progression of AD.Statement of SignificanceAlzheimer’s disease (AD) is the most common neurodegenerative disease with the unclear mechanism of amyloid beta peptide (Aβ). This work have implemented a computational model to address the Ca2+ dynamics of astrocyte mediated by Aβ with the four different pathways: voltage-gated calcium channels, metabotropic glutamate receptors 5, ryanodine receptor channels and membrane leak. The Ca2+ oscillations and bifurcation diagram indicate that astrocytes exhibit ionic excitability mediated by Aβ and become the potential targets of Aβ neurotoxicity. We expect this shared computational model would advance the understanding of AD.

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Effects of compensation, connectivity and tau in a computational model of Alzheimer's Disease

The 2011 International Joint Conference on Neural Networks ◽

10.1109/ijcnn.2011.6033268 ◽

2011 ◽

Cited By ~ 3

Author(s):

Mark Rowan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Computational Model ◽

Model Of Alzheimer’S Disease

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Alzheimer’s Disease as a Result of Stimulus Reduction in a GABA-A-Deficient Brain: A Neurocomputational Model

Neural Plasticity ◽

10.1155/2020/8895369 ◽

2020 ◽

Vol 2020 ◽

pp. 1-26

Author(s):

Mariana Antonia Aguiar-Furucho ◽

Francisco Javier Ropero Peláez

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Computational Model ◽

Sensory Information ◽

Continuous Learning ◽

Sensory Stimuli ◽

Gaba A ◽

Neural Excitability ◽

Sensory Cortices ◽

Synaptic Pruning

Several research studies point to the fact that sensory and cognitive reductions like cataracts, deafness, macular degeneration, or even lack of activity after job retirement, precede the onset of Alzheimer’s disease. To simulate Alzheimer’s disease earlier stages, which manifest in sensory cortices, we used a computational model of the koniocortex that is the first cortical stage processing sensory information. The architecture and physiology of the modeled koniocortex resemble those of its cerebral counterpart being capable of continuous learning. This model allows one to analyze the initial phases of Alzheimer’s disease by “aging” the artificial koniocortex through synaptic pruning, by the modification of acetylcholine and GABA-A signaling, and by reducing sensory stimuli, among other processes. The computational model shows that during aging, a GABA-A deficit followed by a reduction in sensory stimuli leads to a dysregulation of neural excitability, which in the biological brain is associated with hypermetabolism, one of the earliest symptoms of Alzheimer’s disease.

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Pursuing the Complexity of Alzheimer’s Disease: Discovery of Fluoren-9-Amines as Selective Butyrylcholinesterase Inhibitors and N-Methyl-d-Aspartate Receptor Antagonists

Biomolecules ◽

10.3390/biom11010003 ◽

2020 ◽

Vol 11 (1) ◽

pp. 3

Author(s):

Jan Konecny ◽

Anna Misiachna ◽

Martina Hrabinova ◽

Lenka Pulkrabkova ◽

Marketa Benkova ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Nmda Receptor ◽

In Silico ◽

Docking Simulation ◽

Initial Assessment ◽

Unknown Etiology ◽

Cholinesterase Inhibition ◽

Symptomatic Therapy ◽

Receptor Antagonists

Alzheimer’s disease (AD) is a complex disorder with unknown etiology. Currently, only symptomatic therapy of AD is available, comprising cholinesterase inhibitors and N-methyl-d-aspartate (NMDA) receptor antagonists. Drugs targeting only one pathological condition have generated only limited efficacy. Thus, combining two or more therapeutic interventions into one molecule is believed to provide higher benefit for the treatment of AD. In the presented study, we designed, synthesized, and biologically evaluated 15 novel fluoren-9-amine derivatives. The in silico prediction suggested both the oral availability and permeation through the blood–brain barrier (BBB). An initial assessment of the biological profile included determination of the cholinesterase inhibition and NMDA receptor antagonism at the GluN1/GluN2A and GluN1/GluN2B subunits, along with a low cytotoxicity profile in the CHO-K1 cell line. Interestingly, compounds revealed a selective butyrylcholinesterase (BChE) inhibition pattern with antagonistic activity on the NMDARs. Their interaction with butyrylcholinesterase was elucidated by studying enzyme kinetics for compound 3c in tandem with the in silico docking simulation. The docking study showed the interaction of the tricyclic core of new derivatives with Trp82 within the anionic site of the enzyme in a similar way as the template drug tacrine. From the kinetic analysis, it is apparent that 3c is a competitive inhibitor of BChE.

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