Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease: Evidence of impaired glutamatergic neurotransmission?

Lazzaro, Vincenzo Di; Oliviero, Antonio; Pilato, Fabio; Saturno, E.; Dileone, M.; Tonali, P.

doi:10.1002/ana.10600

Cited by 42 publications

(27 citation statements)

References 5 publications

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“…The reduced NMDAR activation and signaling in A␤ 42 -incubated control brain slices and the report showing A␤ oligomers induce NMDAR-dependent long-term depression (LTD) in cultured hippocampal neurons (Shankar et al, 2007) illustrates that A␤ causes NMDAR-dependent synaptic defects in AD individuals and transgenic AD mice with heightened A␤ (Di Lazzaro et al, 2003;Inghilleri et al, 2006;Battaglia et al, 2007). NMDARs clustered in PSD through interaction with synaptic anchoring proteins like PSD-95 (Malenka and Nicoll, 1993).…”

Section: Discussionmentioning

confidence: 99%

Dissociating β-Amyloid from α7 Nicotinic Acetylcholine Receptor by a Novel Therapeutic Agent, S 24795, Normalizes α7 Nicotinic Acetylcholine and NMDA Receptor Function in Alzheimer's Disease Brain

Wang¹,

Stucky²,

Liu³

et al. 2009

J. Neurosci.

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Section: Discussionmentioning

confidence: 99%

Dissociating β-Amyloid from α7 Nicotinic Acetylcholine Receptor by a Novel Therapeutic Agent, S 24795, Normalizes α7 Nicotinic Acetylcholine and NMDA Receptor Function in Alzheimer's Disease Brain

Wang¹,

Stucky²,

Liu³

et al. 2009

J. Neurosci.

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“…Namely, the motor thresholds appear significantly reduced in early stages of the disease, with an initial threshold reduction paralleling disease progression, despite pharmacological treatment [167][168][169][170][171]. In advanced disease, there is a gradual increase of motor thresholds, probably reflecting the underlying cortical neuronal degeneration [172].…”

Section: Utility Of Tms In Alzheimer's Diseasementioning

confidence: 99%

Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

Vucic

Kiernan

2017

Neurotherapeutics

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Transcranial magnetic stimulation (TMS) is a noninvasive technique that has provided important information about cortical function across an array of neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, Parkinson's disease, and related extrapyramidal disorders. Application of TMS techniques in neurodegenerative diseases has provided important pathophysiological insights, leading to the development of pathogenic and diagnostic biomarkers that could be used in the clinical setting and therapeutic trials. Abnormalities of TMS outcome measures heralding cortical hyperexcitability, as evidenced by a reduction of short-interval intracortical inhibition and increased in motorevoked potential amplitude, have been consistently identified as early and intrinsic features of amyotrophic lateral sclerosis (ALS), preceding and correlating with the ensuing neurodegeneration. Cortical hyperexcitability appears to form the pathogenic basis of ALS, mediated by trans-synaptic glutamate-mediated excitotoxic mechanisms. As a consequence of these research findings, TMS has been developed as a potential diagnostic biomarker, capable of identifying upper motor neuronal pathology, at earlier stages of the disease process, and thereby aiding in ALS diagnosis. Of further relevance, marked TMS abnormalities have been reported in other neurodegenerative diseases, which have varied from findings in ALS. With time and greater utilization by clinicians, TMS outcome measures may prove to be of utility in future therapeutic trial settings across the neurodegenerative disease spectrum, including the monitoring of neuroprotective, stem-cell, and genetic-based strategies, thereby enabling assessment of biological effectiveness at early stages of drug development.

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“…Voltage-gated sodium channels are critical to cortical axon excitability12 while excitatory synaptic neurotransmission in the neocortex is mediated by the glutaminergic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (receptors 13. Thus voltage-gated sodium channel blocking drugs increase MT14 15 while glutaminergic agonists decrease it 16. Interestingly, neuromodulatory agents affecting GABA, dopaminergic, noradrenergic and cholinergic systems do not affect the MT 17…”

Section: Introductionmentioning

confidence: 98%

Interrogating cortical function with transcranial magnetic stimulation: insights from neurodegenerative disease and stroke

Agarwal

Koch

Hillis

et al. 2018

J Neurol Neurosurg Psychiatry

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Transcranial magnetic stimulation (TMS) is an accessible, non-invasive technique to study cortical function in vivo. TMS studies have provided important pathophysiological insights across a range of neurodegenerative disorders and enhanced our understanding of brain reorganisation after stroke. In neurodegenerative disease, TMS has provided novel insights into the function of cortical output cells and the related intracortical interneuronal networks. Characterisation of cortical hyperexcitability in amyotrophic lateral sclerosis and altered motor cortical function in frontotemporal dementia, demonstration of cholinergic deficits in Alzheimer's disease and Parkinson's disease are key examples where TMS has led to advances in understanding of disease pathophysiology and potential mechanisms of propagation, with the potential for diagnostic applications. In stroke, TMS methodology has facilitated the understanding of cortical reorganisation that underlie functional recovery. These insights are critical to the development of effective and targeted rehabilitation strategies in stroke. The present review will provide an overview of cortical function measures obtained using TMS and how such measures may provide insight into brain function. Through an improved understanding of cortical function across a range of neurodegenerative disorders, and identification of changes in neural structure and function associated with stroke that underlie clinical recovery, more targeted therapeutic approaches may now be developed in an evolving era of precision medicine.

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Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease: Evidence of impaired glutamatergic neurotransmission?

Cited by 42 publications

References 5 publications

Dissociating β-Amyloid from α7 Nicotinic Acetylcholine Receptor by a Novel Therapeutic Agent, S 24795, Normalizes α7 Nicotinic Acetylcholine and NMDA Receptor Function in Alzheimer's Disease Brain

Dissociating β-Amyloid from α7 Nicotinic Acetylcholine Receptor by a Novel Therapeutic Agent, S 24795, Normalizes α7 Nicotinic Acetylcholine and NMDA Receptor Function in Alzheimer's Disease Brain

Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

Interrogating cortical function with transcranial magnetic stimulation: insights from neurodegenerative disease and stroke

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