Potassium Channels and Internal Calcium Release: Relevance for Memory Storage and Alzheimer’s Disease

Objective. Previous studies have shown that some patients with semantic dementia (SD) have memory storage disorders, while others have access disorders. Here, we report three SD cases with both disorders.Methods. Ten pictures and ten words were prepared as visual stimuli to determine if the patients could correctly answer names and select pictures after hearing the names of items (Card Presentation Task, assessing memory storage disorder). In a second task, the viewing time was set at 20 or 300 msec (Momentary Presentation Task, evaluating memory access disorder) using items for which correct answers were given in the first task. The results were compared with those for 6 patients with Alzheimer’s disease (AD).Results. The SD patients had lower scores than the AD group for both tasks, suggesting both storage and access disorders. The AD group had almost perfect scores on the Card Presentation Task but showed impairment on the Momentary Presentation Task, although to a lesser extent than the SD cases.Conclusions. These results suggest that SD patients have both storage and access disorders and have more severe access disorder than patients with AD.

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Metaplasticity mechanisms restore plasticity and associativity in an animal model of Alzheimer’s disease

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1613700114 ◽

2017 ◽

Vol 114 (21) ◽

pp. 5527-5532 ◽

Cited By ~ 25

Author(s):

Qin Li ◽

Sheeja Navakkode ◽

Martin Rothkegel ◽

Tuck Wah Soong ◽

Sreedharan Sajikumar ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Ryanodine Receptors ◽

Long Term Potentiation ◽

Neuronal Population ◽

Memory Storage ◽

Dynamic Regulation ◽

Model Of Alzheimer’S Disease ◽

Synaptic Tagging And Capture

Dynamic regulation of plasticity thresholds in a neuronal population is critical for the formation of long-term plasticity and memory and is achieved by mechanisms such as metaplasticity. Metaplasticity tunes the synapses to undergo changes that are necessary prerequisites for memory storage under physiological and pathological conditions. Here we discovered that, in amyloid precursor protein (APP)/presenilin-1 (PS1) mice (age 3–4 mo), a prominent mouse model of Alzheimer’s disease (AD), late long-term potentiation (LTP; L-LTP) and its associative plasticity mechanisms such as synaptic tagging and capture (STC) were impaired already in presymptomatic mice. Interestingly, late long-term depression (LTD; L-LTD) was not compromised, but the positive associative interaction of LTP and LTD, cross-capture, was altered in these mice. Metaplastic activation of ryanodine receptors (RyRs) in these neurons reestablished L-LTP and STC. We propose that RyR-mediated metaplastic mechanisms can be considered as a possible therapeutic target for counteracting synaptic impairments in the neuronal networks during the early progression of AD.

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Alzheimer’s disease as the cerebral cortex disorder

Science and Innovations in Medicine ◽

10.35693/2500-1388-2019-4-2-16-20 ◽

2019 ◽

Vol 4 (2) ◽

pp. 16-20

Author(s):

Volobuev AN ◽

Romanchuk PI ◽

Bulgakova SV

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Information Transfer ◽

Brain Cortex ◽

Senile Dementia ◽

Memory Storage ◽

Neuronal Circuits ◽

Storage Element ◽

Dementia Of Alzheimer’S Type ◽

The Brain

Objectives – to highlight the structure, function and localization of Alzheimer’s disease and to specify cognitive impairments related to it. Material and methods. The anatomic data of human brain structure were used. Results. The patterns of memory formation in the brain cortex are investigated. The brain cortex is presented as a type of syncytium consisting of elementary neural structures – cyclic neuronal circuits – memory elements. All cyclic neuronal circuits in a brain cortex are functionally interconnected. The connections between the neuronal circuits can be determined (imprinted) and stochastic (random). The intensity of stochastic communications defines the person's potential for creativity. The impairment of cyclic neuronal circuit connections results in either Alzheimer’s disease or in senile dementia of Alzheimer’s type. Conclusion. In case the cortex is considered as the syncytium, the memory storage element, it can be the reason of the human creativity. It is shown that the failure of the information transfer in the cortex syncytium or neurons destruction in the neuronal network results in Alzheimer’s disease or in senile dementia of Alzheimer’s type.

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Inhibition of potassium channels by 4-aminopyridine prevents the negative feedback modulation of [3H]acetylcholine release in the hippocampus: a possible therapeutic approach in Alzheimer's disease

Pharmacological Research ◽

10.1016/1043-6618(92)90307-w ◽

1992 ◽

Vol 25 ◽

pp. 99-100 ◽

Cited By ~ 1

Author(s):

T. Zelles ◽

A. Gachályi ◽

E.S. Vizi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Potassium Channels ◽

Negative Feedback ◽

Therapeutic Approach ◽

Acetylcholine Release

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The 12th J. A. F. Stevenson Memorial Lecture: Aging, Alzheimer's disease, and the cholinergic system

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y84-123 ◽

1984 ◽

Vol 62 (7) ◽

pp. 741-754 ◽

Cited By ~ 52

Author(s):

Patrick L. McGeer

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Substantia Nigra ◽

Locus Coeruleus ◽

Basal Forebrain ◽

Cholinergic System ◽

Memory Storage ◽

Substantia Nigra Pars Compacta ◽

Memorial Lecture ◽

Reticular Activating System

Aging does not affect tissues in a uniform fashion. Within the brain, substantial neuronal dropout occurs with age in the cholinergic medial basal forebrain complex, the noradrenergic locus coeruleus, and the dopaminergic substantia nigra pars compacta. These areas are also struck by diseases that are sharply age dependent. Alzheimer's disease causes neuronal destruction in the cholinergic cells of the medial basal forebrain and noradrenergic cells of the locus coeruleus. Parkinson's disease causes neuronal destruction mainly in the substantia nigra but with some destruction in the locus coeruleus. Parkinsonism–dementia affects all three areas. Alzheimer's disease is responsible for 50–60% of all cases of dementia. Severe dementia rises in frequency from less than 1% of the population at age 65–70 to over 15% by age 85. The cause of the disease is unknown. No method of prevention is known and present treatments are ineffective, although modest improvement has been reported for various therapeutic regimens designed to stimulate the cholinergic system. The neuronal systems identified as being affected in Alzheimer's disease and in the dementia of Parkinsonism correspond with those shown many years ago to be associated with the reticular activating system. This correspondence permits a new hypothesis of cognition and memory to be put forward, as well as a reinterpretation of data from animal research on the reticular activating system performed over a quarter of a century ago. The locus coeruleus is proposed as the noradrenergic element sensitizing the cortex to conscious recognition of real time events. The medial basal forebrain complex is proposed as the system registering the conscious event for storage and as the readout device when it is subsequently redisplayed in the cortex as memory. Storage could either be in the temporal lobe, in several areas of cortex with feedback to the medial basal forebrain, or in the cholinergic cells themselves.

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Dendritic spines are lost in clusters in Alzheimer’s disease

Scientific Reports ◽

10.1038/s41598-021-91726-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mite Mijalkov ◽

Giovanni Volpe ◽

Isabel Fernaud-Espinosa ◽

Javier DeFelipe ◽

Joana B. Pereira ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dendritic Spines ◽

Neurodegenerative Disorder ◽

Pyramidal Cells ◽

Memory Deficits ◽

Memory Storage ◽

Excitatory Synapses ◽

Tau Pathology ◽

Insight Into

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.

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