Presynaptic failure in Alzheimer's disease

@article{Barthet2020PresynapticFI,
  title={Presynaptic failure in Alzheimer's disease},
  author={Ga{\"e}l Barthet and Christophe Mulle},
  journal={Progress in Neurobiology},
  year={2020},
  volume={194}
}
Synaptic loss is the best correlate of cognitive deficits in Alzheimer's disease (AD). Extensive experimental evidence also indicates alterations of synaptic properties at the early stages of disease progression, before synapse loss and neuronal degeneration. A majority of studies in mouse models of AD have focused on post-synaptic mechanisms, including impairment of long-term plasticity, spine structure and glutamate receptor-mediated transmission. Here we review the literature indicating that… 
Distinctive alteration of presynaptic proteins in the outer molecular layer of the dentate gyrus in Alzheimer’s disease
TLDR
The distinctive vulnerability of the outer molecular layer of the dentate gyrus is highlighted and supports the notion of presynaptic failure in Alzheimer’s disease.
Distinctive alteration of presynaptic proteins in the outer molecular layer of the dentate gyrus in Alzheimer’s disease
TLDR
This study highlights the distinctive vulnerability of the OML of dentate gyrus and supports the notion of presynaptic failure in AD.
APP accumulates around dense-core amyloid plaques with presynaptic proteins in Alzheimer’s disease brain
TLDR
The data supports a role of presynaptic APP in AD pathology and highlights APP accumulations as a potential source of Aβ and Nter peptides to fuel amyloid plaques.
The Role of D-Amino Acids in Alzheimer's Disease.
TLDR
The experimental findings linking D-serine and D-aspartate, through NMDA receptor modulation, to AD and cognitive functions are reported and will facilitate novel therapeutic treatments to cure the disease and improve life expectancy.
Super-resolution microscopy: a closer look at synaptic dysfunction in Alzheimer disease.
TLDR
Critical new insights provided by SRM into the molecular architecture and dynamic organization of the synapse and, in particular, the interactions between Aβ and tau in this compartment are reviewed.
GABAB Receptors and Cognitive Processing in Health and Disease.
  • S. Vlachou
  • Medicine
    Current topics in behavioral neurosciences
  • 2021
TLDR
Results indicate a possible therapeutic role of GABAB receptor compounds for the treatment of cognitive dysfunction and learning/memory impairments for some of these conditions, especially in neurodegeneration.
Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner
TLDR
It is found that FERMT2 directly interacts with APP to modulate its metabolism and that FerMT2 under-expression impacts axonal growth, synaptic connectivity and long-term potentiation in an APP-dependent manner.
Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner
TLDR
It is found that FERMT2 directly interacts with APP to modulate its metabolism, and that FerMT2 underexpression impacts axonal growth, synaptic connectivity, and long-term potentiation in an APP-dependent manner.
Aplysia Neurons as a Model of Alzheimer's Disease: Shared Genes and Differential Expression.
TLDR
The marine snail Aplysia californica offers a unique and underutilized system in which to study the physiological, behavioral, and molecular impacts of AD, and its ramifications are suggested to underpin cognitive declines in aging and neurodegeneration.
Proteomic insights into synaptic signaling in the brain: the past, present and future
TLDR
The findings of proteomic studies of chemical synapses in the brain are reviewed, with special attention paid to the key players in synaptic signaling, i.e., the synaptic protein complexes and their post-translational modifications.
...
1
2
3
...

References

SHOWING 1-10 OF 168 REFERENCES
Early synaptic deficits in the APP/PS1 mouse model of Alzheimer's disease involve neuronal adenosine A2A receptors
TLDR
In the APP/PS1 mouse model of AD amyloidosis, it is shown that associative long-term synaptic potentiation (LTP) is abolished in CA3 pyramidal cells at an early stage, and treatment with A2AR antagonists reverts one-trial memory deficits.
Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease
TLDR
Transmission electron microscopy data show region-specific changes in synaptic mitochondria in AD and support the idea that the transport of mitochondria to presynaptic terminals or synaptic mitochondrial dynamics may be altered in AD.
The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease
TLDR
It is suggested that synaptic changes are central to the disease process, and that the march of neurofibrillary tangles through brain circuits appears to take advantage of recently described mechanisms of transsynaptic spread of pathological forms of tau.
Synapses and Alzheimer's disease.
TLDR
The mechanisms underlying these processes are beginning to be elucidated, and, although their relevance to AD remains debated, understanding these processes will likely allow new therapeutic avenues to AD.
Synaptic loss in Alzheimer's disease and other dementias
TLDR
All AD patients showed a striking decrease in synaptic staining in the outer half of the molecular layer of the dentate gyrus compared with control brains, where the density of synaptic terminals was uniform throughout.
Intracellular Ca2+ stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer’s disease
TLDR
It is shown that neuronal hyperactivity is a hallmark of healthy aging but is further aggravated by AD-related mutations in presenilin 1 protein, and store emptying normalized neuronal network activity in mutant mice, identifying presynaptic Ca2+ stores as a key element controlling AD- related neuronal hyper activity and as a target for disease-modifying treatments.
Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses
TLDR
Observations suggest that endogenous Aβ peptides have a crucial role in activity-dependent regulation of synaptic vesicle release and might point to the primary pathological events that lead to compensatory synapse loss in Alzheimer's disease.
β-Amyloid Causes Depletion of Synaptic Vesicles Leading to Neurotransmission Failure*
TLDR
It is found that similar to other pore-forming neurotoxins, Aβ induced a rapid increase in intracellular calcium and miniature currents, indicating an enhancement in vesicular transmitter release, indicating that Aβ blocks neurotransmission by causing vesicle depletion.
Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein
TLDR
The impaired synaptic plasticity in APP deficient mice is associated with abnormal neuronal morphology and synaptic function within the hippocampus, andaired-pulse depression of GABA-mediated inhibitory post-synaptic currents was attenuated in APP-null mice.
Presynaptic and Postsynaptic Interaction of the Amyloid Precursor Protein Promotes Peripheral and Central Synaptogenesis
TLDR
In vitro and in vivo studies identify APP as a novel synaptic adhesion molecule and postulate that transsynaptic APP interaction modulates its synaptic function and that perturbed APP synapticAdhesion activity may contribute to synaptic dysfunction and AD pathogenesis.
...
1
2
3
4
5
...