Alzheimer's disease: An evolving understanding of noradrenergic involvement and the promising future of electroceutical therapies

Slater, Cody; Wang, Qi

doi:10.1002/ctm2.397

Cited by 22 publications

(13 citation statements)

References 273 publications

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“…Recent findings further highlighted the prevalence of cerebrovascular disorders in Down syndrome patients and added to a growing body of evidence implicating cerebrovascular abnormalities as a core feature of AD rather than a simple comorbidity [ 7 ]. Moreover, adrenergic system, including α/β adrenergic receptors and their downstream molecular signaling process, might serve as the key approach to modulate these cerebrovascular abnormalities and progressive neurodegeneration [ 8 ]. In this review, we summarized the interplay between cerebrovascular function and AD pathologies in both AD animal models and AD patients.…”

Section: Introductionmentioning

confidence: 99%

Involvement of cerebrovascular abnormalities in the pathogenesis and progression of Alzheimer’s disease: an adrenergic approach

Song

Che

Wang

et al. 2021

Aging

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Alzheimer’s disease (AD), as the most common neurodegenerative disease in elder population, is pathologically characterized by β-amyloid (Aβ) plaques, neurofibrillary tangles composed of highly-phosphorylated tau protein and consequently progressive neurodegeneration. However, both Aβ and tau fails to cover the whole pathological process of AD, and most of the Aβ- or tau-based therapeutic strategies are all failed. Increasing lines of evidence from both clinical and preclinical studies have indicated that age-related cerebrovascular dysfunctions, including the changes in cerebrovascular microstructure, blood-brain barrier integrity, cerebrovascular reactivity and cerebral blood flow, accompany or even precede the development of AD-like pathologies. These findings may raise the possibility that cerebrovascular changes are likely pathogenic contributors to the onset and progression of AD. In this review, we provide an appraisal of the cerebrovascular alterations in AD and the relationship to cognitive impairment and AD pathologies. Moreover, the adrenergic mechanisms leading to cerebrovascular and AD pathologies were further discussed. The contributions of early cerebrovascular factors, especially through adrenergic mechanisms, should be considered and treasured in the diagnostic, preventative, and therapeutic approaches to address AD.

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Section: Introductionmentioning

confidence: 99%

Involvement of cerebrovascular abnormalities in the pathogenesis and progression of Alzheimer’s disease: an adrenergic approach

Song

Che

Wang

et al. 2021

Aging

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“…Vagus nerve stimulation’s ability to activate the LC-NE system has long been hypothesized to underlie, in part, the clinical benefits of VNS ( Slater and Wang, 2021 ). VNS is thought to activate the LC via the vagus nerve’s afferent projections to the nucleus tractus solitarius (NTS) ( Van Bockstaele et al, 1999 ; Ruffoli et al, 2011 ).…”

Section: Vagus Nerve Stimulation Activates Multiple Neuromodulatory S...mentioning

confidence: 99%

Rapid Effects of Vagus Nerve Stimulation on Sensory Processing Through Activation of Neuromodulatory Systems

2022

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After sensory information is encoded into neural signals at the periphery, it is processed through multiple brain regions before perception occurs (i.e., sensory processing). Recent work has begun to tease apart how neuromodulatory systems influence sensory processing. Vagus nerve stimulation (VNS) is well-known as an effective and safe method of activating neuromodulatory systems. There is a growing body of studies confirming VNS has immediate effects on sensory processing across multiple sensory modalities. These immediate effects of VNS on sensory processing are distinct from the more well-documented method of inducing lasting neuroplastic changes to the sensory pathways through repeatedly delivering a brief VNS burst paired with a sensory stimulus. Immediate effects occur upon VNS onset, often disappear upon VNS offset, and the modulation is present for all sensory stimuli. Conversely, the neuroplastic effect of pairing sub-second bursts of VNS with a sensory stimulus alters sensory processing only after multiple pairing sessions, this alteration remains after cessation of pairing sessions, and the alteration selectively affects the response properties of neurons encoding the specific paired sensory stimulus. Here, we call attention to the immediate effects VNS has on sensory processing. This review discusses existing studies on this topic, provides an overview of the underlying neuromodulatory systems that likely play a role, and briefly explores the potential translational applications of using VNS to rapidly regulate sensory processing.

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“…However, despite the evidence of LC degeneration in AD, its contribution to pathology was underappreciated for years. Recently, several reports have studied the role of the noradrenergic system in AD and highlighted its potential as a therapeutic target [ 13 , 14 , 15 , 16 ]. Nevertheless, the role of the noradrenergic system in AD remains unclear, and controversial studies about NA pointed out both to neuroprotective and neurotoxic actions in AD.…”

Section: Introductionmentioning

confidence: 99%

Noradrenaline in Alzheimer’s Disease: A New Potential Therapeutic Target

Gutiérrez

Russo

Novellino

et al. 2022

IJMS

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A growing body of evidence demonstrates the important role of the noradrenergic system in the pathogenesis of many neurodegenerative processes, especially Alzheimer’s disease, due to its ability to control glial activation and chemokine production resulting in anti-inflammatory and neuroprotective effects. Noradrenaline involvement in this disease was first proposed after finding deficits of noradrenergic neurons in the locus coeruleus from Alzheimer’s disease patients. Based on this, it has been hypothesized that the early loss of noradrenergic projections and the subsequent reduction of noradrenaline brain levels contribute to cognitive dysfunctions and the progression of neurodegeneration. Several studies have focused on analyzing the role of noradrenaline in the development and progression of Alzheimer’s disease. In this review we summarize some of the most relevant data describing the alterations of the noradrenergic system normally occurring in Alzheimer’s disease as well as experimental studies in which noradrenaline concentration was modified in order to further analyze how these alterations affect the behavior and viability of different nervous cells. The combination of the different studies here presented suggests that the maintenance of adequate noradrenaline levels in the central nervous system constitutes a key factor of the endogenous defense systems that help prevent or delay the development of Alzheimer’s disease. For this reason, the use of noradrenaline modulating drugs is proposed as an interesting alternative therapeutic option for Alzheimer’s disease.

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Alzheimer's disease: An evolving understanding of noradrenergic involvement and the promising future of electroceutical therapies

Cited by 22 publications

References 273 publications

Involvement of cerebrovascular abnormalities in the pathogenesis and progression of Alzheimer’s disease: an adrenergic approach

Involvement of cerebrovascular abnormalities in the pathogenesis and progression of Alzheimer’s disease: an adrenergic approach

Rapid Effects of Vagus Nerve Stimulation on Sensory Processing Through Activation of Neuromodulatory Systems

Noradrenaline in Alzheimer’s Disease: A New Potential Therapeutic Target

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