scholarly journals Computer Model of Synapse Loss During an Alzheimer’s Disease-like Pathology in Hippocampal Subregions DG, CA3 and CA1—the Way to Chaos and Information Transfer

Entropy ◽  
2019 ◽  
Vol 21 (4) ◽  
pp. 408 ◽  
Author(s):  
Świetlik ◽  
Białowąs ◽  
Moryś ◽  
Kusiak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lyapunov Exponent ◽  
Information Flow ◽  
Shannon Entropy ◽  
Control Model ◽  
Maximal Lyapunov Exponent ◽  
Synapse Loss ◽  
Entropy Transfer ◽  
Pathological Model

The aim of the study was to compare the computer model of synaptic breakdown in an Alzheimer’s disease-like pathology in the dentate gyrus (DG), CA3 and CA1 regions of the hippocampus with a control model using neuronal parameters and methods describing the complexity of the system, such as the correlative dimension, Shannon entropy and positive maximal Lyapunov exponent. The model of synaptic breakdown (from 13% to 50%) in the hippocampus modeling the dynamics of an Alzheimer’s disease-like pathology was simulated. Modeling consisted in turning off one after the other EC2 connections and connections from the dentate gyrus on the CA3 pyramidal neurons. The pathological model of synaptic disintegration was compared to a control. The larger synaptic breakdown was associated with a statistically significant decrease in the number of spikes (R = −0.79, P < 0.001), spikes per burst (R = −0.76, P < 0.001) and burst duration (R = −0.83, P < 0.001) and an increase in the inter-burst interval (R = 0.85, P < 0.001) in DG-CA3-CA1. The positive maximal Lyapunov exponent in the control model was negative, but in the pathological model had a positive value of DG-CA3-CA1. A statistically significant decrease of Shannon entropy with the direction of information flow DG->CA3->CA1 (R = −0.79, P < 0.001) in the pathological model and a statistically significant increase with greater synaptic breakdown (R = 0.24, P < 0.05) of the CA3-CA1 region was obtained. The reduction of entropy transfer for DG->CA3 at the level of synaptic breakdown of 35% was 35%, compared with the control. Entropy transfer for CA3->CA1 at the level of synaptic breakdown of 35% increased to 95% relative to the control. The synaptic breakdown model in an Alzheimer’s disease-like pathology in DG-CA3-CA1 exhibits chaotic features as opposed to the control. Synaptic breakdown in which an increase of Shannon entropy is observed indicates an irreversible process of Alzheimer’s disease. The increase in synapse loss resulted in decreased information flow and entropy transfer in DG->CA3, and at the same time a strong increase in CA3->CA1.

scholarly journals Effects of Inducing Gamma Oscillations in Hippocampal Subregions DG, CA3, and CA1 on the Potential Alleviation of Alzheimer’s Disease-Related Pathology: Computer Modeling and Simulations

Entropy ◽  
2019 ◽  
Vol 21 (6) ◽  
pp. 587
Author(s):  
Dariusz Świetlik ◽  
Jacek Białowąs ◽  
Janusz Moryś ◽  
Ilona Klejbor ◽  
Aida Kusiak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Pyramidal Neurons ◽  
Gamma Oscillations ◽  
Control Model ◽  
Transfer Entropy ◽  
Ca1 Region ◽  
Pathological Model ◽  
The One

The aim of this study was to evaluate the possibility of the gamma oscillation function (40–130 Hz) to reduce Alzheimer’s disease related pathology in a computer model of the hippocampal network dentate gyrus, CA3, and CA1 (DG-CA3-CA1) regions. Methods: Computer simulations were made for a pathological model in which Alzheimer’s disease was simulated by synaptic degradation in the hippocampus. Pathology modeling was based on sequentially turning off the connections with entorhinal cortex layer 2 (EC2) and the dentate gyrus on CA3 pyramidal neurons. Gamma induction modeling consisted of simulating the oscillation provided by the septo-hippocampal pathway with band frequencies from 40–130 Hz. Pathological models with and without gamma induction were compared with a control. Results: In the hippocampal regions of DG, CA3, and CA1, and jointly DG-CA3-CA1 and CA3-CA1, gamma induction resulted in a statistically significant improvement in terms of increased numbers of spikes, spikes per burst, and burst duration as compared with the model simulating Alzheimer’s disease (AD). The positive maximal Lyapunov exponent was negative in both the control model and the one with gamma induction as opposed to the pathological model where it was positive within the DG-CA3-CA1 region. Gamma induction resulted in decreased transfer entropy in accordance with the information flow in DG → CA3 and CA3 → CA1. Conclusions: The results of simulation studies show that inducing gamma oscillations in the hippocampus may reduce Alzheimer’s disease related pathology. Pathologically higher transfer entropy values after gamma induction returned to values comparable to the control model.

scholarly journals Computer Modeling of Alzheimer’s Disease—Simulations of Synaptic Plasticity and Memory in the CA3-CA1 Hippocampal Formation Microcircuit

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1909
Author(s):  
Dariusz Świetlik ◽  
Jacek Białowąs ◽  
Janusz Moryś ◽  
Ilona Klejbor ◽  
Aida Kusiak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Computer Modeling ◽  
Hippocampal Formation ◽  
Pyramidal Cells ◽  
Control Model ◽  
Pathological Model ◽  
Ca3 Pyramidal Cells ◽  
And Control

This paper aims to present computer modeling of synaptic plasticity and memory in the CA3-CA1 hippocampal formation microcircuit. The computer simulations showed a comparison of a pathological model in which Alzheimer’s disease (AD) was simulated by synaptic degradation in the hippocampus and control model (healthy) of CA3-CA1 networks with modification of weights for the memory. There were statistically higher spike values of both CA1 and CA3 pyramidal cells in the control model than in the pathological model (p = 0.0042 for CA1 and p = 0.0033 for CA3). A similar outcome was achieved for frequency (p = 0.0002 for CA1 and p = 0.0001 for CA3). The entropy of pyramidal cells of the healthy CA3 network seemed to be significantly higher than that of AD (p = 0.0304). We need to study a lot of physiological parameters and their combinations of the CA3-CA1 hippocampal formation microcircuit to understand AD. High statistically correlations were obtained between memory, spikes and synaptic deletion in both CA1 and CA3 cells.

scholarly journals APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Zhao ◽  
Yuan Fu ◽  
Yu Yamazaki ◽  
Yingxue Ren ◽  
Mary D. Davis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Subject ◽  
Late Onset ◽  
Disease Patient ◽  
Underlying Mechanism ◽  
Synapse Loss ◽  
Induced Pluripotent ◽  
Human Ipsc ◽  
Normal Cognition

Abstract APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer’s disease (AD). To address the underlying mechanism, we develop cerebral organoid models using induced pluripotent stem cells (iPSCs) with APOE ε3/ε3 or ε4/ε4 genotype from individuals with either normal cognition or AD dementia. Cerebral organoids from AD patients carrying APOE ε4/ε4 show greater apoptosis and decreased synaptic integrity. While AD patient-derived cerebral organoids have increased levels of Aβ and phosphorylated tau compared to healthy subject-derived cerebral organoids, APOE4 exacerbates tau pathology in both healthy subject-derived and AD patient-derived organoids. Transcriptomics analysis by RNA-sequencing reveals that cerebral organoids from AD patients are associated with an enhancement of stress granules and disrupted RNA metabolism. Importantly, isogenic conversion of APOE4 to APOE3 attenuates the APOE4-related phenotypes in cerebral organoids from AD patients. Together, our study using human iPSC-organoids recapitulates APOE4-related phenotypes and suggests APOE4-related degenerative pathways contributing to AD pathogenesis.

scholarly journals Direction of Information Flow in Alzheimer's Disease and MCI Patients

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Fabrizio Vecchio ◽  
Claudio Babiloni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Information Flow ◽  
Additive Model ◽  
Functional Coupling ◽  
Directed Transfer Function ◽  
Directional Flow ◽  
Eeg Data ◽  
Rest Condition ◽  
Amnesic Mild Cognitive Impairment

Is directionality of electroencephalographic (EEG) synchronization abnormal in amnesic mild cognitive impairment (MCI) and Alzheimer's disease (AD)? And, do cerebrovascular and AD lesions represent additive factors in the development of MCI as a putative preclinical stage of AD? Here we reported two studies that tested these hypotheses. EEG data were recorded in normal elderly (Nold), amnesic MCI, and mild AD subjects at rest condition (closed eyes). Direction of information flow within EEG electrode pairs was performed by directed transfer function (DTF) atδ(2–4 Hz),θ(4–8 Hz),α1 (8–10 Hz),α2 (10–12 Hz),β1 (13–20 Hz),β2 (20–30 Hz), andγ(30–40 Hz). Parieto-to-frontal direction was stronger in Nold than in MCI and/or AD subjects forαandβrhythms. In contrast, the directional flow within interhemispheric EEG functional coupling did not discriminate among the groups. More interestingly, this coupling was higher atθ,α1,α2, andβ1 in MCI with higher than in MCI with lower vascular load. These results suggest that directionality of parieto-to-frontal EEG synchronization is abnormal not only in AD but also in amnesic MCI, supporting the additive model according to which MCI state would result from the combination of cerebrovascular and neurodegenerative lesions.

scholarly journals VAMP2 is a cerebrospinal fluid marker of selective hippocampal synapse loss and episodic memory performance in Alzheimer’s disease

2020 ◽  
Vol 16 (S4) ◽  
Author(s):  
Olivia Belbin ◽  
Beatriu Molina ◽  
Raúl Núñez‐Llaves ◽  
Julie Goossens ◽  
Nele Dewit ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Episodic Memory ◽  
Memory Performance ◽  
Synapse Loss

scholarly journals Neurocognitive predictors of financial capacity across the dementia spectrum: Normal aging, mild cognitive impairment, and Alzheimer’s disease

2009 ◽  
Vol 15 (2) ◽  
pp. 258-267 ◽  
Author(s):  
MEGAN G. SHEROD ◽  
H. RANDALL GRIFFITH ◽  
JACQUELYNN COPELAND ◽  
KATHERINE BELUE ◽  
SARA KRZYWANSKI ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Aging ◽  
Control Model ◽  
Cognitive Models ◽  
Story Recall ◽  
Financial Capacity

AbstractFinancial capacity is a complex instrumental activity of daily living critical to independent functioning of older adults and sensitive to impairment in patients with amnestic mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, little is known about the neurocognitive basis of financial impairment in dementia. We developed cognitive models of financial capacity in cognitively healthy older adults (n = 85) and patients with MCI (n = 113) and mild AD (n = 43). All participants were administered the Financial Capacity Instrument (FCI) and a neuropsychological test battery. Univariate correlation and multiple regression procedures were used to develop cognitive models of overall FCI performance across groups. The control model (R2 = .38) comprised (in order of entry) written arithmetic skills, delayed story recall, and simple visuomotor sequencing. The MCI model (R2 = .69) comprised written arithmetic skills, visuomotor sequencing and set alternation, and race. The AD model (R2 = .65) comprised written arithmetic skills, simple visuomotor sequencing, and immediate story recall. Written arithmetic skills (WRAT-3 Arithmetic) was the primary predictor across models, accounting for 27% (control model), 46% (AD model), and 55% (MCI model) of variance. Executive function and verbal memory were secondary model predictors. The results offer insight into the cognitive basis of financial capacity across the dementia spectrum of cognitive aging, MCI, and AD. (JINS, 2009, 15, 258–267.)

Synapse loss in the temporal lobe in Alzheimer's disease

1993 ◽  
Vol 33 (2) ◽  
pp. 190-199 ◽  
Author(s):  
Scheff W. Scheff ◽  
Douglas A. Price
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Synapse Loss

scholarly journals Inhibitory synapse loss and accumulation of amyloid beta in inhibitory presynaptic terminals in Alzheimer’s disease

2021 ◽  
Author(s):  
Hatice Kurucu ◽  
Martí Colom‐Cadena ◽  
Caitlin Davies ◽  
Lewis Wilkins ◽  
Declan King ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Inhibitory Synapse ◽  
Presynaptic Terminals ◽  
Synapse Loss
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