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https://www.readbyqxmd.com/read/28927263/molecular-and-cellular-basis-of-neurodegeneration-in-alzheimer-s-disease
#1
Sangyun Jeong
The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid beta-peptide (Abeta) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than Abeta plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28910085/cholesterol-changes-the-mechanisms-of-a%C3%AE-peptide-binding-to-the-dmpc-bilayer
#2
Christopher Lockhart, Dmitri K Klimov
Using isobaric-isothermal all-atom replica-exchange molecular dynamics (REMD) simulations, we investigated the equilibrium binding of Aβ10-40 monomers to the zwitterionic dimyristoylphosphatidylcholine (DMPC) bilayer containing cholesterol. Our previous REMD simulations, which studied binding of the same peptide to the cholesterol-free DMPC bilayer, served as a control, against which we measured the impact of cholesterol. Our findings are as follows. First, addition of cholesterol to the DMPC bilayer partially expels the Aβ peptide from the hydrophobic core and promotes its binding to bilayer polar headgroups...
October 2, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28882310/studying-tau-protein-propagation-and-pathology-in-the-mouse-brain-using-adeno-associated-viruses
#3
Susanne Wegmann, Rachel E Bennett, Ana S Amaral, Bradley T Hyman
The progressive spread of pathological brain lesions containing aggregated tau protein is a hallmark of Alzheimer's disease and other neurodegenerative diseases. In AD, this process follows a distinct pattern along neuronal connections from the entorhinal cortex to hippocampal areas and further on through the limbic system. In other tauopathies, the spread of tau appears less hierarchical throughout the brain, and also nonpathological tau is reported to cross-synaptic connections in the brain. To be able to study the process of cell-to-cell transport of tau and the associated neurotoxicity in the brain in vivo, adeno-associated virus-mediated expression of tau can be used to express different forms of tau in distinct brain areas in rodent models...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28691712/erratum-reduction-of-abeta-amyloid-pathology-in-appps1-transgenic-mice-in-the-absence-of-gut-microbiota
#4
T Harach, N Marungruang, N Duthilleul, V Cheatham, K D Mc Coy, G Frisoni, J J Neher, F Fåk, M Jucker, T Lasser, T Bolmont
This corrects the article DOI: 10.1038/srep41802.
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625940/prodromal-stage-of-disease-dementia-with-lewy-bodies-how-to-diagnose-in-practice
#5
Frédéric Blanc, Marc Verny
Disease with Lewy bodies or dementia with Lewy bodies (DLB), particularly at the prodromal stage, is a complex disease to diagnose because of different clinical beginnings and variable paths in terms of clinical expression. Thus DLB can be entcountered in different input modes: mild cognitive impairment, depression, acute behavioral disorders, confusion and delirium, or sleep disorders. In the aim to better diagnose the disease, should be sought obviously to search for the key symptoms: fluctuations, hallucinations, extra-pyramidal syndrome, and REM sleep behavior disorder...
June 1, 2017: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
https://www.readbyqxmd.com/read/28495580/novel-curcumin-loaded-nanoparticles-engineered-for-blood-brain-barrier-crossing-and-able-to-disrupt-abeta-aggregates
#6
Ruozi Barbara, Daniela Belletti, Francesca Pederzoli, Martina Masoni, Johannes Keller, Antonio Ballestrazzi, Maria Angela Vandelli, Giovanni Tosi, Andreas M Grabrucker
The formation of extracellular aggregates built up by deposits of β-amyloid (Aβ) is a hallmark of Alzheimer's disease (AD). Curcumin has been reported to display anti-amyloidogenic activity, not only by inhibiting the formation of new Aβ aggregates, but also by disaggregating existing ones. However, the uptake of Curcumin into the brain is severely restricted by its low ability to cross the blood-brain barrier (BBB). Therefore, novel strategies for a targeted delivery of Curcumin into the brain are highly desired...
May 8, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28403230/isoflurane-anesthesia-promotes-cognitive-impairment-by-inducing-expression-of-%C3%AE-amyloid-protein-related-factors-in-the-hippocampus-of-aged-rats
#7
Shuai Zhang, Xueyuan Hu, Wei Guan, Li Luan, Bei Li, Qichao Tang, Honggang Fan
Isoflurane anesthesia has been shown to be responsible for cognitive impairment in Alzheimer's disease (AD) and development of AD in the older age groups. However, the pathogenesis of AD-related cognitive impairments induced by isoflurane anesthesia remains elusive. Thus, this study was designed to investigate the mechanism by which isoflurane anesthesia caused AD-related cognitive impairments. Aged Wistar rats were randomly divided into 6 groups (n = 12), 1 control group (CONT) and 5 isoflurane treated (ISO) groups (ISO 0, ISO 0...
2017: PloS One
https://www.readbyqxmd.com/read/28387900/the-relationship-between-intracranial-pressure-and-neurocognitive-function-before-and-after-the-repair-of-a-skull-injury
#8
J He, L-L Chen, D-K Sun, H-T Wang, J-J Wang, X Zhai
OBJECTIVE: This study examines the relationship between intracranial pressure (ICP) changes after skull injury repair and neurocognitive function before and after the repair. PATIENTS AND METHODS: Sixty patients undergoing skull injury repair participated in the study. A non-invasive detection analyzer was used to detect the ICP 2 days before operation, 10 days after the operation and one month after the operation in all patients. Additionally, the mean cerebral blood flow velocities (MV) in the internal carotid and the medial cerebral arteries were detected using a transcranial Doppler ultrasound (TCD)...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28328043/csf-tau-and-the-csf-tau-abeta-ratio-for-the-diagnosis-of-alzheimer-s-disease-dementia-and-other-dementias-in-people-with-mild-cognitive-impairment-mci
#9
REVIEW
Craig Ritchie, Nadja Smailagic, Anna H Noel-Storr, Obioha Ukoumunne, Emma C Ladds, Steven Martin
BACKGROUND: Research suggests that measurable change in cerebrospinal fluid (CSF) biomarkers occurs years in advance of the onset of clinical symptoms (Beckett 2010). In this review, we aimed to assess the ability of CSF tau biomarkers (t-tau and p-tau) and the CSF tau (t-tau or p-tau)/ABeta ratio to enable the detection of Alzheimer's disease pathology in patients with mild cognitive impairment (MCI). These biomarkers have been proposed as important in new criteria for Alzheimer's disease dementia that incorporate biomarker abnormalities...
March 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28318364/defective-retrograde-transport-impairs-autophagic-clearance-in-alzheimer-disease-neurons
#10
Prasad Tammineni, Qian Cai
Macroautophagy/autophagy plays a key role in cellular quality control by eliminating protein aggregates and damaged organelles, which is essential for the maintenance of neuronal homeostasis. Defective autophagy has been implicated in the pathogenesis of Alzheimer disease (AD). In AD brains, autophagic vacuoles (AVs) accumulate massively within dystrophic neurites. This raises a fundamental question as to whether impaired autophagic clearance contributes to AD-associated autophagic stress. We recently revealed that AD neurons display defective retrograde transport and accumulation of amphisomes predominantly in axons and presynaptic terminals...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28298292/cellular-cholesterol-homeostasis-in-alzheimer-s-disease
#11
Ta Yuan Chang, Yoshio Yamauchi, Mazahir T Hasan, Catherine Cy Chang
Alzheimer's disease [AD] is the most common form of dementia in older adults. Currently, there is no cure for AD. The hallmark of AD is the accumulation of extracellular amyloid plaques composed of amyloid beta peptides [Abeta; especially Abeta1-42], and neurofibrillary tangles, composed of hyper-phosphorylated tau, accompanied with chronic neuroinflammation. Abeta are derived from the amyloid precursor protein APP. The oligomeric form of Abeta is probably the most neurotoxic species; its accumulation eventually forms the insoluble and aggregated amyloid plaques...
March 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28238790/multifunctional-liposomes-interact-with-abeta-in-human-biological-fluids-therapeutic-implications-for-alzheimer-s-disease
#12
Elisa Conti, Maria Gregori, Isabella Radice, Fulvio Da Re, Denise Grana, Francesca Re, Elisa Salvati, Massimo Masserini, Carlo Ferrarese, Chiara Paola Zoia, Lucio Tremolizzo
The accumulation of extracellular amyloid beta (Abeta42) both in brain and in cerebral vessels characterizes Alzheimer's disease (AD) pathogenesis. Recently, the possibility to functionalize nanoparticles (NPs) surface with Abeta42 binding molecules, making them suitable tools for reducing Abeta42 burden has been shown effective in models of AD. Aim of this work consisted in proving that NPs might be effective in sequestering Abeta42 in biological fluids, such as CSF and plasma. This demonstration is extremely important considering that these Abeta42 pools are in continuum with the brain parenchyma with drainage of Abeta from interstitial brain tissue to blood vessel and plasma...
February 24, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28237964/vulnerability-of-primary-neurons-derived-from-tg2576-alzheimer-mice-to-oxygen-and-glucose-deprivation-role-of-intraneuronal-amyloid-%C3%AE-accumulation-and-astrocytes
#13
Vito Antonio Baldassarro, Alessandra Marchesini, Luciana Giardino, Laura Calzà
Microvascular dysfunction is considered an integral part of Alzheimer disease (AD) pathogenesis, but the possible relationship between amyloid pathology, microvascular dysfunction and cell death is still unclear. In order to investigate the influence of intraneuronal amyloid-β (Aβ) accumulation on vulnerability to hypoxia, we isolated primary cortical neurons from Tg2576 (carrying the amyloid precursor protein APPSwe mutation) and wild-type fetal mice. We first demonstrated that neurons isolated from Tg2576 newborn mice show an increase in VEGFa mRNA expression and a decrease in the expression of the two VEGF receptors, Flt1 and Kdr, compared with wild-type cells...
May 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28186729/n-terminal-hypothesis-for-alzheimer-s-disease
#14
Brian Murray, Bhanushee Sharma, Georges Belfort
Although the amyloid (abeta peptide, Aβ) hypothesis is 25 years old, is the dominant model of Alzheimer's disease (AD) pathogenesis, and guides the development of potential treatments, it is still controversial. One possible reason is a lack of a mechanistic path from the cleavage products of the amyloid precursor protein (APP) such as soluble Aβ monomer and soluble molecular fragments to the deleterious effects on synaptic form and function. From a review of the recent literature and our own published work including aggregation kinetics and structural morphology, Aβ clearance, molecular simulations, long-term potentiation measurements with inhibition binding, and the binding of a commercial monoclonal antibody, aducanumab, we hypothesize that the N-terminal domains of neurotoxic Aβ oligomers are implicated in causing the disease...
February 10, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28183246/solid-state-structure-of-abeta-a%C3%AE-in-alzheimer-s-disease
#15
REVIEW
Jun-Xia Lu, Xing-Qi Dong, Jian-Jun Zhang
Alzheimer's disease (AD) has become the most common neurodegenerative disease. The deposition of amyloid fibrils in the brain is one of the characteristics of AD. The fibrils are composed of amyloid-β peptide (Aβ). Aβ is produced through a series event of protease cleavage of a transmembrane protein called β-amyloid precursor protein (APP) which is commonly expressed in the brain. The production of Aβ and its propensity to aggregation to form oligomers and fibrils are believed to initiate a sequence of events that lead to AD dementia...
2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28176819/reduction-of-abeta-amyloid-pathology-in-appps1-transgenic-mice-in-the-absence-of-gut-microbiota
#16
T Harach, N Marungruang, N Duthilleul, V Cheatham, K D Mc Coy, G Frisoni, J J Neher, F Fåk, M Jucker, T Lasser, T Bolmont
Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28028177/autophagy-mediated-regulation-of-bace1-protein-trafficking-and-degradation
#17
Tuancheng Feng, Prasad Tammineni, Chanchal Agrawal, Yu Young Jeong, Qian Cai
β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the major neuronal β-secretase for amyloid-β generation and is degraded in lysosomes. The autophagy-lysosomal system plays a key role in the maintenance of cellular homeostasis in neurons. Recent studies established that nascent autophagosomes in distal axons move predominantly in the retrograde direction toward the soma, where mature lysosomes are mainly located. However, it remains unknown whether autophagy plays a critical role in regulation of BACE1 trafficking and degradation...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27807401/alzheimer-disease-crosstalk-between-the-canonical-wnt-beta-catenin-pathway-and-ppars-alpha-and-gamma
#18
REVIEW
Alexandre Vallée, Yves Lecarpentier
The molecular mechanisms underlying the pathophysiology of Alzheimer's disease (AD) are still not fully understood. In AD, Wnt/beta-catenin signaling has been shown to be downregulated while the peroxisome proliferator-activated receptor (PPAR) gamma (mARN and protein) is upregulated. Certain neurodegenerative diseases share the same Wnt/beta-catenin/PPAR gamma profile, such as bipolar disorder and schizophrenia. Conversely, other NDs share an opposite profile, such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, multiple sclerosis, and Friedreich's ataxia...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27572805/re-engineering-therapeutic-antibodies-for-alzheimer-s-disease-as-blood-brain-barrier-penetrating-bi-specific-antibodies
#19
REVIEW
William M Pardridge
Therapeutic antibodies are large molecule drugs that do not cross the blood-brain barrier (BBB). Therefore, drug development of therapeutic antibodies for Alzheimer's disease (AD) requires that these molecules be re-engineered to enable BBB delivery. This is possible by joining the therapeutic antibody with a transporter antibody, resulting in the engineering of a BBB-penetrating bispecific antibody (BSA). Areas covered: The manuscript covers transporter antibodies that cross the BBB via receptor-mediated transport systems on the BBB, such as the insulin receptor or transferrin receptor...
December 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27459792/-effects-of-aluminium-chloride-on-the-methylation-of-app-in-hippocampal-of-rats
#20
Xiaojuan Yang, Yuzhou Yuan, Qiao Niu
OBJECTIVE: To study the effect of aluminum chloride on amyloid precursor protein ( APP ) promoter methylation and the content of amyloid beta-protein (Abeta) in hippocampus of rats. METHODS: Forty male SPF grade SD rats were divided into four groups: control group (0.9% NaCl), 10 mg/kg AlCl3 group, 20 mg/kg AlCl3 group, and 30 mg/kg AlCl3 group, respectively. After treatment for 8 weeks, the APP methylation level and expressions of APP mRNA was detected by methylation specific PCR and quantitative real time PCR, respectively...
May 2016: Wei Sheng Yan Jiu, Journal of Hygiene Research
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