Inhibitory interneurons in Alzheimer’s disease

Vargová, Gréta; Vogels, Thomas; Kostecká, Z.; Hromádka, Tomáš

doi:10.4149/bll_2018_038

Cited by 8 publications

(6 citation statements)

References 54 publications

(60 reference statements)

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“…What is clear in NCLs is that AFSMs are deposited in lysosomes, and their function is impaired; as it seems, the preserved normal lysosomal function is critical for the proper functioning of interneurons [ 47 , 92 ]. Interestingly, interneuron populations have also been shown to play an important role in the neurodegenerative pathways of various diseases, such as epilepsy [ 93 ], Alzheimer’s [ 94 ], amyotrophic lateral sclerosis (ALS) [ 95 ], and Parkinson’s [ 96 ].…”

Section: Genetics and Pathophysiologymentioning

confidence: 99%

Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis

Kaminiów

Kozak

Paprocka

2022

IJMS

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Neuronal ceroid lipofuscinoses (NCLs) are a group of rare, inherited, neurodegenerative lysosomal storage disorders that affect children and adults. They are traditionally grouped together, based on shared clinical symptoms and pathological ground. To date, 13 autosomal recessive gene variants, as well as one autosomal dominant gene variant, of NCL have been described. These genes encode a variety of proteins, whose functions have not been fully defined; most are lysosomal enzymes, transmembrane proteins of the lysosome, or other organelles. Common symptoms of NCLs include the progressive loss of vision, mental and motor deterioration, epileptic seizures, premature death, and, in rare adult-onset cases, dementia. Depending on the mutation, these symptoms can vary, with respect to the severity and onset of symptoms by age. Currently, all forms of NCL are fatal, and no curative treatments are available. Herein, we provide an overview to summarize the current knowledge regarding the pathophysiology, genetics, and clinical manifestation of these conditions, as well as the approach to diagnosis.

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Section: Genetics and Pathophysiologymentioning

confidence: 99%

Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis

Kaminiów

Kozak

Paprocka

2022

IJMS

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“…However, interneurons are also essential to the nor-mal functioning of the neuronal network. Forming around 20% of the total neuronal network, 3 most interneurons are γ-aminobutyric acid (GABA)ergic and inhibitory, also acting as a source of neuropeptides that help to regulate cortical function. 4 There are three main classes of the inhibitory interneuron with calcium-binding proteins and neuropeptides used to distinguish between them.…”

Section: Introductionmentioning

confidence: 99%

Histological characterization of interneurons in Alzheimer's disease reveals a loss of somatostatin interneurons in the temporal cortex

et al. 2020

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Neuronal dysfunction and synaptic loss are major hallmarks of Alzheimer's disease (AD) which correlate with symptom severity. Impairment of the γ‐aminobutyric acid (GABA)ergic inhibitory interneurons, which form around 20% of the total neuronal network, may be an early event contributing to neuronal circuit dysfunction in neurodegenerative diseases. This study examined the expression of two of the main classes of inhibitory interneurons, parvalbumin (PV) and somatostatin (SST) interneurons in the temporal cortex and hippocampus of AD and control cases, using immunohistochemistry. We report a significant regional variation in the number of PV and SST interneurons with a higher number identified per mm2 in the temporal cortex compared to the hippocampus. Fewer SST interneurons, but not PV interneurons, were identified per mm2 in the temporal cortex of AD cases compared to control subjects. Our results support regional neuroanatomical effects on selective interneuron classes in AD, and suggest that impairment of the interneuronal circuit may contribute to neuronal dysfunction and cognitive decline in AD.

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“…Tau pathology is additionally accompanied by chronic neuroinflammation, with reactive microglia and astrocytes [8]. The entire pathological process ultimately culminates in dysfunction of neuronal networks, resulting in progressive cognitive impairment [9].…”

Section: Introductionmentioning

confidence: 99%

Viral Delivery of Non-Mutated Human Truncated Tau to Neurons Recapitulates Key Features of Human Tauopathy in Wild-Type Mice

Vogels

Vargová

Brezováková

et al. 2020

JAD

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Background: Neuronal accumulation of hyperphosphorylated and truncated tau aggregates is one of the major defining factors and key drivers of neurodegeneration in Alzheimer’s disease and other tauopathies. Objective: We developed an AAV-induced model of tauopathy mediated by human truncated tau protein without familial frontotemporal dementia-related mutations to study tau propagation and the functional consequences of tau pathology. Methods: We performed targeted transductions of the hippocampus or entorhinal cortex in adult mice followed by histological analysis to study the progression of hippocampal tau pathology and tau spreading. We performed behavioral analysis of mice with AAV-induced hippocampal tau pathology. Results: AAV-induced hippocampal tau pathology was characterized by tau hyperphosphorylation (AT8 positivity), sarkosyl insolubility, and the presence of neurofibrillary tangles. AAV-induced tau pathology was associated with microgliosis and hypertrophic astrocytes in the absence of cognitive deficits. Additionally, the co-expression of mCherry fluorescent protein and human truncated tau enabled us to detect both local spreading of human tau and spreading from the entorhinal cortex to the synaptically connected dentate gyrus. Conclusion: Targeted delivery of AAV with truncated tau protein into subcortical and cortical structures of mammalian brains represents an efficient approach for creating temporally and spatially well-defined tau pathology suitable for in vivo studies of tau propagation and neuronal circuit deficits in Alzheimer’s disease.

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Inhibitory interneurons in Alzheimer’s disease

Cited by 8 publications

References 54 publications

Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis

Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis

Histological characterization of interneurons in Alzheimer's disease reveals a loss of somatostatin interneurons in the temporal cortex

Viral Delivery of Non-Mutated Human Truncated Tau to Neurons Recapitulates Key Features of Human Tauopathy in Wild-Type Mice

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