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Current Alzheimer Research

David S Xu, Francisco Ponce
High-frequency deep brain stimulation (DBS) is a neurosurgical procedure that was introduced in the late 1980s for the treatment of movement disorders. It is a reversible, adjustable, and non-ablative therapy that has been used in over 100,000 people worldwide. The surgical procedure used to implant the DBS system, as well as the effects of chronic electrical stimulation, have been shown to be safe and effective through many clinical trials. The ability to therapeutically modulate the motor circuits of the brain in this manner has resulted in consideration of use of this surgical strategy for other neurodegenerative and neuropsychiatric disorders involving non-motor circuits, including appetite, mood, and cognition...
October 14, 2016: Current Alzheimer Research
Michele Zorzetto, Francesca Datturi, Laura Divizia, Cristiana Pistono, Ilaria Campo, Annalisa De Silvestri, Mariaclara Cuccia, Giovanni Ricevuti
BACKGROUND/OBJECTIVES: Increasing evidence suggests the importance of neuroinflammation in the pathogenesis of Alzheimer's disease (AD), which is a complex neurodegenerative disorder. Complement activation occurs in the brain of patients with AD and seems to contribute to an important local inflammatory state. Increased expression of the fourth serum complement component 4 (C4) has been observed in AD patients in many studies. This protein has two isoforms, encoded by two genes: C4A and C4B localized to the HLA class III region...
October 12, 2016: Current Alzheimer Research
Noemí Arce-Varas, Giulia Abate, Chiara Prandelli, Carmen Martínez, Fernando Cuetos, Manuel Menéndez, Mariagrazia Marziano, David Cabrera-García, María Teresa Fernández-Sánchez, Antonello Novelli, Maurizio Memo, Daniela Uberti
Many studies suggest oxidative stress as an early feature of Alzheimer's Disease (AD). However, evidence of established oxidative stress in AD peripheral cells is still inconclusive, possibly due to both, differences in the type of samples and the heterogeneity of oxidative markers used in different studies. Here we measured the activity of Superoxide Dismutase, Catalase and Glutathione Peroxidase both in the extracellular and the intracellular blood compartments of AD, MCI and control subjects. The amount of an open isoform of p53 protein (unfolded p53), resulting from oxidative modifications was also determined...
October 10, 2016: Current Alzheimer Research
Allal Boutajangout, Abdulwahab Noorwali, Hazem Atta, Thomas Wisniewski
INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia. The search for new treatments is made more urgent given its increasing prevalence resulting from the aging of the global population. Over the past two decades, stem cell technologies have become an increasingly attractive option to both study and potentially treat neurodegenerative diseases. Several investigators reported a beneficial effect of different types of stem or progenitor cells on the pathology and cognitive function in AD models...
October 4, 2016: Current Alzheimer Research
Boris Decourt, Debomoy K Lahiri, Marwan N Sabbagh
Alzheimer's disease (AD) affects an estimated 44 million individuals worldwide, yet no therapeutic intervention is available to stop the progression of the dementia. Neuropathological hallmarks of AD are extracellular deposits of amyloid beta (Aβ) peptides into plaques, intraneuronal accumulation of hyperphosphorylated tau protein forming tangles, and chronic inflammation. A pivotal molecule in inflammation is the pro-inflammatory cytokine TNF-α. Several lines of evidence using genetic and pharmacological manipulations indicate that TNF-α signaling exacerbates both Aβ and tau pathologies in vivo...
September 30, 2016: Current Alzheimer Research
David Hsu, Gad A Marshall
The field of Alzheimer disease (AD) prevention has been a culmination of basic science, clinical, and translational research. In the past three years since the new 2011 AD diagnostic guidelines, large-scale collaborative efforts have embarked on new clinical trials with the hope of someday preventing AD. This review will shed light on the historical and scientific contexts in which these trials were based on, as well as discuss potential challenges these trials may face in the coming years. Primary preventive measures, such as lifestyle, multidomain, medication, and supplemental interventions, will be analyzed...
September 30, 2016: Current Alzheimer Research
Asante R Kamkwalala, Paul A Newhouse
The major components of the cholinergic receptor system of the human brain include projections from the basal forebrain nuclei, and utilize the two types of receptors that they synapse on, nicotinic and muscarinic acetylcholine receptors. With the widespread cortical and subcortical projections of the basal forebrain, activity of these two receptor systems provide modulation of neurotransmitter activity underlying normal cognitive processes, such as attention, episodic memory, and working memory. Alzheimer's disease (AD) targets and damages cholinergic neurons in the basal forebrain, and as these projections are lost, cognitive performance progressively declines...
September 30, 2016: Current Alzheimer Research
Irene Gonsalvez, Roey Baror, Peter Fried, Emiliano Santarnecchi, Alvaro Pascual-Leone
Alzheimer's disease (AD) is a looming public health crisis that currently lacks an effective treatment. Noninvasive Brain Stimulation (NBS), particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), offers a promising alternative approach to pharmacological interventions for an increasing number of neurological and psychiatric conditions. The aim of this review is summarize data from therapeutic trials of NBS in AD and other dementing illnesses. Despite the potential of NBS, there is limited theoretical framework and a lack of guidelines for its applications to AD...
September 30, 2016: Current Alzheimer Research
J Budni, M L Garcez, J de Medeiros, E Cassaro, T Santos-Bellettini, F Mina, J Quevedo
Alzheimer's disease (AD) is a neurodegenerative disorder, the most common form of dementia in elderly. Although, AD has been discovered over a century ago, the drugs approved by the US Food and Drug Administration are not yet fully effective in the AD treatment. Current evidence suggests that the antibiotic minocycline could be a potential therapeutic drug for use in the AD treatment due to its anti-neuroinflammatory effects. Here, we provide a review of the pre-clinical and clinical studies about minocycline and we discussed the treatment timing and its dosage, as well as effect of minocycline on brain markers and its possible mechanism in AD...
August 19, 2016: Current Alzheimer Research
Ewelina Maliszewska-Cyna, Madelaine Lynch, Jonathan Jordan Oore, Paul Michael Nagy, Isabelle Aubert
Alzheimer's disease (AD) is a degenerative disorder characterized by neuronal and vascular dysfunction and progressive cognitive decline. Furthermore, deficits in cerebral glucose metabolism and insulin resistance are being increasingly recognized in AD pathology. Many lifestyle-modifying approaches, including diet and exercise, have yielded promising results in modulating brain morphology and function for the prevention and early treatment of AD. This review focuses on the effects of physical exercise on rescuing cognition and limiting the progression of AD pathology...
August 19, 2016: Current Alzheimer Research
Vincent Villette, Patrick Dutar
The early phase of Alzheimer's disease (AD) involves the disruption of finely tuned neuronal circuitry in brain regions associated with learning and memory. This tuning is obtained from the delicate balance of excitatory and inhibitory inputs which regulate cortical network function. This homeostatic plasticity provides a dynamic basis for appropriate information transfer in the brain. Excitatory synaptic transmission is driven mainly by glutamatergic synapses whereas inhibitory synaptic transmission involves GABAergic and glycinergic signaling...
August 19, 2016: Current Alzheimer Research
Keran Ma, JoAnne McLaurin
Alzheimer's disease (AD) is characterized by accumulation and aggregation of beta-amyloid peptide, neurofibrillary tangles of hyperphosphorylated tau, neuroinflammation, synaptic degeneration and eventual neuronal cell loss. Current treatment options for AD provide temporary symptomatic relief in a subset of patients. These drugs include cholinesterase inhibitors that improve cholinergic innervation such as rivastigmine, donepezil and galatamine. In addition, memantine, a N-methyl-D-aspartate antagonist, is used to treat moderate to severe AD by reducing excitotoxicity...
August 19, 2016: Current Alzheimer Research
Siddhartha Mondragón-Rodríguez, George Perry, Fernando Peña-Ortega, Sylvain Williams
The last two decades have seen a great advance in the data that supports the two current hypotheses in Alzheimer's disease (AD) field, the amyloid beta (Aβ) hypothesis and the tau hypothesis. Not surprisingly, Aβ and tau proteins are currently the major therapeutic research targets for AD treatment. Unfortunately, nothing but moderate success has emerged from such therapeutic approaches. With this in mind, we will discuss deep brain stimulation (DBS) as a promising therapeutic strategy that aims to restore brain activity...
August 19, 2016: Current Alzheimer Research
Brian T Reed, Francine Behar-Cohen, Slavica Krantic
Alzheimer's disease (AD) develops undetected for years due to the lack of early diagnostic biomarkers. In advanced AD, visual deficits related to cortical neurodegeneration are well recognized, but recent studies have identified that the retina could be affected prior to vulnerable brain areas such as cortex and hippocampus. In this review, we focus on new evidence suggesting that synaptic dysfunction within the retina may be reminiscent of changes within the brain. The data on the earliest dysfunction of synaptic and neuronal networks in vulnerable brain areas (mostly cortex and hippocampus) are next discussed to point out how they may inspire the analogous research in the retina during the asymptomatic stage of AD...
August 19, 2016: Current Alzheimer Research
Paulami Chatterjee, Debjani Roy
BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease throughout the world. Most of the clinical symptoms of AD appear at a very later stage, therefore, the identification of disease markers is essential which can help proper detection of AD at an earlier stage and slow down its progression. Studies have implicated that epigenetic biomarkers, such as DNA methylation, histone modification and non coding RNA mediated regulation serve crucial roles in several disease progression including AD...
August 3, 2016: Current Alzheimer Research
Lihua Qiu, Yong He, Hehan Tang, Yi Zhou, Jinhong Wang, Weiwei Zhang, Guangxiang Chen, Fei Zhao, Tingxue Ouyang, Bin Ju, Zhengyan Li, Lanlan Wang, Ling Zou, Qiyong Gong
: Several genome-wide association studies have found that the rs11136000 polymorphism of the C allele (CLU-C) is associated with the risk for developing late-onset Alzheimer's disease (LOAD). However, the effects of the CLU-C/C genotype on brain structure, including gray and white matter, are not adequately understood. OBJECTIVES: We aimed to clarify the gray matter and white matter integrity changes in non-demented ageing individuals with the AD risk gene of the rs11136000 polymorphism of the C allele (CLU-C) and the correlation with cognitive performance...
July 3, 2016: Current Alzheimer Research
Yuan Liao, Xiao-Lan Qi, Ying Cao, Wen-Feng Yu, Rivka Ravid, Bengt Winblad, Jin-Jing Pei, Zhi-Zhong Guan
The purpose of this study was to investigate the alterations in the levels of nuclear factor κBp65 (NF-κBp65), monocyte chemoattractant protein 1 (MCP-1/CCL-2) and macrophage inflammatory protein 1α (MIP-1α/CCL-3) in relationship to the expression of α3 nicotinic acetylcholine receptor (nAChR) during the pathogenesis of Alzheimer's disease (AD). The post-mortem human brains of AD and age-matched control individuals, SH-SY5Y and U87MG cell lines exposed to β-amyloid peptide (Aβ), as well as the SH-SY5Y cells in which α3 nAChR was down-regulated by siRNA were used to study the possible expression changes of the targets such as NF-κBp65, MCP-1, MIP-1α and α3 nAChR...
July 3, 2016: Current Alzheimer Research
Charlotte Griffioen, Eva G Willems, Bettina S Husebo, Wilco P Achterberg
AIM: To describe the prevalence of opioid use in persons with a cognitive impairment compared with cognitively intact persons and to explore factors associated with opioid prescription. METHOD: A search was made in PubMed (Medline), Embase, Cochrane, Central, Cinahl, PsychInfo and Web of Science and additional articles were identified by manual search of reference lists. Titles and abstracts were screened and eligible articles reviewed in full-text. A citation check was performed on the included articles for a complete search...
June 28, 2016: Current Alzheimer Research
Carlos A Sánchez-Catasús, Gilles N Stormezand, Peter Jan van Laar, Peter P De Deyn, Mario Alvarez Sánchez, Rudi A J O Dierckx
This review article aims at providing a state-of-the-art review of the role of fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging (FDG-PET) in the prediction of Alzheimer's dementia in subjects suffering mild cognitive impairment (MCI), with a particular focus on the predictive power of FDG-PET compared to structural magnetic resonance imaging (sMRI). We also address perfusion single photon emission computed tomography (SPECT) as a less costly and more accessible alternative to FDG- PET. A search in PubMed was performed, taking into consideration relevant scientific articles published in English within the last five years and limited to human studies...
June 28, 2016: Current Alzheimer Research
Murat Köseoğlu, Bağdeser Akdoğan Özdilek, Umidahan Djakbarova, Ayse Gülüsürc
Several studies suggest that soluble Amyloid β (Aβ) oligomer-induced aberrant neuronal cell cycle re-entry is the initial trigger for a significant part of the neuronal degeneration and loss in Alzheimer's disease (AD). In this study, we investigated the role of Ras, which is a well-known proto-oncoprotein, in soluble Aβ oligomer- induced aberrant neuronal cell cycle activation and subsequent cell loss using retinoic acid differentiated human SH-SY5Y neuroblastoma cells as model system. In line with previous literature, we showed that in vitro preparations of soluble Aβ42 oligomers triggered cell cycle activation but not cell proliferation...
June 24, 2016: Current Alzheimer Research
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