Synaptic abnormalities are a cardinal feature of Alzheimer's disease (AD) that are known to arise as the disease progresses. A growing body of evidence suggests that pathological alterations to neuronal circuits and synapses may provide a mechanistic link between amyloid β (Aβ) and tau pathology and thus may serve as an obligatory relay of the cognitive impairment in AD. Brain-derived neurotrophic factors (BDNFs) play an important role in maintaining synaptic plasticity in learning and memory. Considering AD as a synaptic disorder, BDNF has attracted increasing attention as a potential diagnostic biomarker and a therapeutical molecule for AD. Although depletion of BDNF has been linked with Aβ accumulation, tau phosphorylation, neuroinflammation and neuronal apoptosis, the exact mechanisms underlying the effect of impaired BDNF signaling on AD are still unknown. Here, we present an overview of how BDNF genomic structure is connected to factors that regulate BDNF signaling. We then discuss the role of BDNF in AD and the potential of BDNF-targeting therapeutics for AD. 

/pdf/brain-derived-neurotrophic-factor-in-alzheimers-disease-and-3to8r9k6.pdf

Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential

/pdf/brain-derived-neurotrophic-factor-in-alzheimers-disease-and-1o0fqp1m.pdf

Paeonol: pharmacological effects and mechanisms of action.

Genus Paeonia: A comprehensive review on traditional uses, phytochemistry, pharmacological activities, clinical application, and toxicology.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory deficits, cognitive decline and spatial disorientation, which seriously endangers human health The role of non-pharmacological interventions to treat AD has been reported in many meta analyses (MAs), but robust conclusions have not been made due to variations in the scope, quality and findings of these reviews Objective: To provide an overview of existing evidence on the effects of non-pharmacological interventions in AD patients on three outcomes: mini-mental state examination (MMSE), activities of daily living (ADL) and Alzheimer’s disease assessment scale-cognitive section (ADAS-cog) by a review of existing MAs Methods: The databases PubMed, Cochrane Library, Embase, and Web of Science were searched to collect MAs of non-pharmacological interventions for AD Literature screening, data extraction, and quality assessment were independently conducted by 2 reviewers We assessed the quality of MAs with the AMSTAR-2 tool, and assessed the evidence quality for significant outcomes using the grading of recommendations assessment, development and evaluation (GRADE) system Results: We found ten eligible MAs which included between three (133 patients) and 15 randomized trials (1217 patients) Contains 5 non-pharmacological interventions, namely acupuncture therapy (40%), exercise intervention (30%), music therapy (10%), cognitive intervention (10%), repetitive transcranial magnetic stimulation(rTMS) (10%) All of the included MAs were of critically low quality to low quality with the AMSTAR-2 tool Acupuncture therapy and exercise intervention show preliminary potential to improve ADL and MMSE rTMS and acupuncture therapy show benefits in decreasing ADAs-cog And there is some evidence of improved MMSE with cognitive intervention All of these outcomes scored very low quality to moderate quality of evidence on the GRADE system Conclusions: Non-pharmacological therapy has a promising prospect for the treatment of AD, but there is still a lack of high-quality evidence In future, the quality of the original research needs to be improved and strict designed MA should be carried out in accordance with the methodological requirements

/pdf/overview-of-meta-analyses-of-five-non-pharmacological-ksrjslxl50.pdf

Overview of Meta-Analyses of Five Non-pharmacological Interventions for Alzheimer's Disease.

Repetitive transcranial magnetic stimulation (rTMS) is a well known non-invasive brain stimulation procedure which is capable of inducing the expression of the hippocampal BDNF that has been already shown to exert significant neuroprotective and pro-cognitive effects in AD. However, it is nearly impossible directly to evaluate the BDNF expression in humans after rTMS application. Here we summarized the underlying mechanisms of the neuroprotective and procognitive effect of BDNF that can be induced through a region-specific rTMS approach. Additionally, we have also evaluated the role of Magnetic Resonance Spectroscopy in monitoring the BDNF response after rTMS application in Alzheimer's Disease. We have provided strong evidence that rTMS exerts significant neuroprotective and pro-cognitive effects through the expression of hippocampal BDNF. Furthermore, Magnetic Resonance Spectroscopy might play a critical role in monitoring the BDNF response after rTMS application in AD patients. Such a sophisticated approach might be able to enlighten us on the time-dependent cognitive and neuroprotective correlates of the rtMS application in AD patients.

Beyond The Therapeutic Effect of rTMS in Alzheimer's Disease: A Possible Neuroprotective Role of Hippocampal BDNF? : A Minireview.

The therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in parkinsonian visual hallucinations: Electrophysiological correlates.

The therapeutic approaches currently applied in Alzheimer's disease (AD) and similar neurodegenerative diseases are essentially based on pharmacological strategies. However, despite intensive research, the effectiveness of these treatments is limited to transient symptomatic effects, and they are still far from exhibiting a true therapeutic effect capable of altering prognosis. The lack of success of such pharmacotherapy-based protocols may be derived from the cases in the majority of trials being too advanced to benefit significantly in therapeutic terms at the clinical level. For neurodegenerative diseases, mild cognitive impairment (MCI) may be an early stage of the disease continuum, including Alzheimer's. Noninvasive brain stimulation (NIBS) techniques have been developed to modulate plasticity in the human cortex in the last few decades. NIBS techniques have made it possible to obtain unique findings concerning brain functions, and design novel approaches to treat various neurological and psychiatric conditions. In addition, its synaptic and cellular neurobiological effects, NIBS is an attractive treatment option in the early phases of neurodegenerative diseases, such as MCI, with its beneficial modifying effects on cellular neuroplasticity. However, there is still insufficient evidence about the potential positive clinical effects of NIBS on MCI. Furthermore, the huge variability of the clinical effects of NIBS limits its use. In this article, we reviewed the combinatory approach of NIBS with various neuroimaging and electrophysiological methods. Such methodologies may provide a new horizon to the path for personalized treatment, including a more individualized pathophysiology approach which might even define new specific targets for specific symptoms of neurodegenerations.

Neuroimaging-Guided Transcranial Magnetic and Direct Current Stimulation in MCI: Toward an Individual, Effective and Disease-Modifying Treatment.

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Beyond The Therapeutic Effect of rTMS in Alzheimer's Disease: A Possible Neuroprotective Role of Hippocampal BDNF? : A Minireview.

The therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in parkinsonian visual hallucinations: Electrophysiological correlates.

Neuroimaging-Guided Transcranial Magnetic and Direct Current Stimulation in MCI: Toward an Individual, Effective and Disease-Modifying Treatment.