How glutamatergic synapse loss affects the firing rhythm of DG-CA3 model related with Alzheimer’s disease

2021 ◽  
Author(s):  
Han Dong ◽  
XiaoLi Yang ◽  
ZhongKui Sun
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamatergic Synapse ◽  
Synapse Loss

scholarly journals Protecting synapses from amyloid β-associated degeneration by manipulations of Wnt/planar cell polarity signaling

2020 ◽  
Author(s):  
Bo Feng ◽  
Andiara E. Freitas ◽  
Runyi Tian ◽  
Yeo Rang Lee ◽  
Akumbir S. Grewal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Planar Cell Polarity ◽  
Synapse Formation ◽  
Amyloid Β ◽  
Glutamatergic Synapse ◽  
Aβ Oligomers ◽  
Synapse Loss ◽  
Synapse Maintenance ◽  
Pcp Signaling

ABSTRACTSynapse loss is an early event in Alzheimer’s disease and is thought to be associated with amyloid pathology and caused by Amyloid β (Aβ) oligomers. Whether and how Aβ oligomers directly target signaling pathways for glutamatergic synapse maintenance is unknown. Glutamatergic synapse development is controlled by the opposing functions of Celsr3 and Vangl2, core components of the Wnt/planar cell polarity (PCP) signaling pathway, functioning directly in the synapses. Celsr3 promotes synapse formation, whereas Vangl2 inhibits synapse formation. Here we show that oligomeric Aβ binds to Celsr3 and assists Vangl2 in disassembling synapses by disrupting the intercellular Celsr3/Frizzled3-Celsr3 complex, essential for PCP signaling. Together with Vangl2, a Wnt receptor, Ryk, is also required for Aβ oligomer-induced synapse loss in a mouse model of Alzheimer’s disease, 5XFAD, where conditional Ryk knockout protected synapses and preserved cognitive function. Our study reveals a fine balance of Wnt/PCP signaling components in glutamatergic synapse maintenance and suggests that overproduced Aβ oligomers may lead to excessive synapse loss by tipping this balance. Together with previous reports that an inhibitor of Wnt/Ryk signaling, WIF1, is found reduced in Alzheimer’s disease patients, our results suggest that the imbalance of PCP signaling in these patients may contribute to synapse loss in Alzheimer’s disease and manipulating Wnt/PCP signaling may preserve synapses and cognitive function.

scholarly journals The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease

2015 ◽  
Vol 6 (2) ◽  
pp. 131 ◽  
Author(s):  
Carolyn C. Rudy ◽  
Holly C. Hunsberger ◽  
Daniel S. Weitzner ◽  
Miranda N. Reed
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamatergic Synapse

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 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

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

Human tau filaments induce microtubule and synapse loss in an in vivo model of neurofibrillary degenerative disease

2000 ◽  
Vol 113 (8) ◽  
pp. 1373-1387 ◽  
Author(s):  
G.F. Hall ◽  
B. Chu ◽  
G. Lee ◽  
J. Yao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intracellular Transport ◽  
Degenerative Disease ◽  
In Vivo Model ◽  
Filament Formation ◽  
Synapse Loss ◽  
Central Neurons ◽  
Cytoskeletal Disruption

The intracellular accumulation of tau protein and its aggregation into filamentous deposits is the intracellular hallmark of neurofibrillary degenerative diseases such as Alzheimer's Disease and familial tauopathies in which tau is now thought to play a critical pathogenic role. Until very recently, the lack of a cellular model in which human tau filaments can be experimentally generated has prevented direct investigation of the causes and consequences of tau filament formation in vivo. In this study, we show that human tau filaments formed in lamprey central neurons (ABCs) that chronically overexpress human tau resemble the ‘straight filaments’ seen in Alzheimer's Disease and other neurofibrillary conditions, and are distinguishable from neurofilaments by their ultrastructure, distribution and intracellular behavior. We also show that tau filament formation in ABCs is associated with a distinctive pattern of dendritic degeneration that closely resembles the cytopathology of human neurofibrillary degenerative disease. This pattern includes localized cytoskeletal disruption and aggregation of membranous organelles, distal dendritic beading, and the progressive loss of dendritic microtubules and synapses. These results suggest that tau filament formation may be responsible for many key cytopathological features of neurofibrillary degeneration, possibly via the loss of microtubule based intracellular transport.

scholarly journals Stimulation-Dependent Intraspinal Microtubules and Synaptic Failure in Alzheimer's Disease: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Fuyuki Mitsuyama ◽  
Yoshio Futatsugi ◽  
Masato Okuya ◽  
Tsukasa Kawase ◽  
Kostadin Karagiozov ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Change ◽  
Cognitive Deficits ◽  
Postsynaptic Membrane ◽  
Structural Mechanism ◽  
Synapse Loss ◽  
Synaptic Failure

There are many microtubules in axons and dendritic shafts, but it has been thought that there were fewer microtubules in spines. Recently, there have been four reports that observed the intraspinal microtubules. Because microtubules originate from the centrosome, these four reports strongly suggest a stimulation-dependent connection between the nucleus and the stimulated postsynaptic membrane by microtubules. In contrast, several pieces of evidence suggest that spine elongation may be caused by the polymerization of intraspinal microtubules. This structural mechanism for spine elongation suggests, conversely, that the synapse loss or spine loss observed in Alzheimer’s disease may be caused by the depolymerization of intraspinal microtubules. Based on this evidence, it is suggested that the impairment of intraspinal microtubules may cause spinal structural change and block the translocation of plasticity-related molecules between the stimulated postsynaptic membranes and the nucleus, resulting in the cognitive deficits of Alzheimer's disease.

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