scholarly journals CA1 pyramidal neuron gene expression mosaics in the Ts65Dn murine model of Down syndrome and Alzheimer's disease following maternal choline supplementation

Hippocampus ◽  
2018 ◽  
Vol 28 (4) ◽  
pp. 251-268 ◽  
Author(s):  
Melissa J. Alldred ◽  
Helen M. Chao ◽  
Sang Han Lee ◽  
Judah Beilin ◽  
Brian E. Powers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Murine Model ◽  
Pyramidal Neuron ◽  
Ca1 Pyramidal Neuron

scholarly journals Increased excitatory to inhibitory synaptic ratio in parietal cortex samples from individuals with Alzheimer’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Julie C. Lauterborn ◽  
Pietro Scaduto ◽  
Conor D. Cox ◽  
Anton Schulmann ◽  
Gary Lynch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Parietal Cortex ◽  
Direct Evidence ◽  
Synaptic Membranes ◽  
Post Mortem ◽  
Expression Studies ◽  
Gene Expression Studies

AbstractSynaptic disturbances in excitatory to inhibitory (E/I) balance in forebrain circuits are thought to contribute to the progression of Alzheimer’s disease (AD) and dementia, although direct evidence for such imbalance in humans is lacking. We assessed anatomical and electrophysiological synaptic E/I ratios in post-mortem parietal cortex samples from middle-aged individuals with AD (early-onset) or Down syndrome (DS) by fluorescence deconvolution tomography and microtransplantation of synaptic membranes. Both approaches revealed significantly elevated E/I ratios for AD, but not DS, versus controls. Gene expression studies in an independent AD cohort also demonstrated elevated E/I ratios in individuals with AD as compared to controls. These findings provide evidence of a marked pro-excitatory perturbation of synaptic E/I balance in AD parietal cortex, a region within the default mode network that is overly active in the disorder, and support the hypothesis that E/I imbalances disrupt cognition-related shifts in cortical activity which contribute to the intellectual decline in AD.

scholarly journals Proteomic interrogation of human hippocampal CA1 pyramidal neuron sublayers in Alzheimer’s disease

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Isabel Reyes ◽  
Evgeny Kanshin ◽  
Beatrix Ueberheide ◽  
Arjun V. Masurkar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pyramidal Neuron ◽  
Hippocampal Ca1 ◽  
Ca1 Pyramidal Neuron

scholarly journals Analysis of Age-Dependent Alterations in Excitability Properties of CA1 Pyramidal Neurons in an APPPS1 Model of Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Paola Vitale ◽  
Ana Rita Salgueiro-Pereira ◽  
Carmen Alina Lupascu ◽  
Michael Willem ◽  
Rosanna Migliore ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Pyramidal Neuron ◽  
Amyloid Β ◽  
Clear Correlation ◽  
Neuron Excitability ◽  
Model Of Alzheimer’S Disease ◽  
Age Dependent ◽  
Ca1 Pyramidal Neuron

Age-dependent accumulation of amyloid-β, provoking increasing brain amyloidopathy, triggers abnormal patterns of neuron activity and circuit synchronization in Alzheimer’s disease (AD) as observed in human AD patients and AD mouse models. Recent studies on AD mouse models, mimicking this age-dependent amyloidopathy, identified alterations in CA1 neuron excitability. However, these models generally also overexpress mutated amyloid precursor protein (APP) and presenilin 1 (PS1) and there is a lack of a clear correlation of neuronal excitability alterations with progressive amyloidopathy. The active development of computational models of AD points out the need of collecting such experimental data to build a reliable disease model exhibiting AD-like disease progression. We therefore used the feature extraction tool of the Human Brain Project (HBP) Brain Simulation Platform to systematically analyze the excitability profile of CA1 pyramidal neuron in the APPPS1 mouse model. We identified specific features of neuron excitability that best correlate either with over-expression of mutated APP and PS1 or increasing Aβ amyloidopathy. Notably, we report strong alterations in membrane time constant and action potential width and weak alterations in firing behavior. Also, using a CA1 pyramidal neuron model, we evidence amyloidopathy-dependent alterations in Ih. Finally, cluster analysis of these recordings showed that we could reliably assign a trace to its correct group, opening the door to a more refined, less variable analysis of AD-affected neurons. This inter-disciplinary analysis, bringing together experimentalists and modelers, helps to further unravel the neuronal mechanisms most affected by AD and to build a biologically plausible computational model of the AD brain.

Sign in / Sign up

Export Citation Format

Share Document