Abstract:
:The identification and characterization of amyloid-beta (Abeta) and tau as the main pathological substrates of Alzheimer's disease (AD) have driven many efforts in search for suitable biomarkers for AD. In the last decade, research in this area has focused on developing a better understanding of the principles that govern protein deposition, mechanisms that link aggregation to toxicity and neuronal death, and a better understanding of protein dynamics in brain tissue, interstitial fluid and CSF. While Abeta and tau represent the two key pathological mediators of disease, other aspects of this multifaceted disease (e.g. oxidative stress, calcium-mediated toxicity, and neuroinflammation) are being unraveled, with the hope to develop a more comprehensive approach in exploring disease mechanisms. This has not only expanded possible areas for disease-modifying therapies, but has also allowed the introduction of novel, and potentially useful, fluid and radiological markers for the presence and progression of AD pathology. There is no doubt that the identification of several fluid and imaging biomarkers that can reliably detect the early stages of AD will have great implications in the design of clinical trials, in the selection of homogenous research populations, and in the assessment of disease outcomes. Markers with good diagnostic specificity will aid researchers in differentiating individuals with preclinical and probable AD from individuals who do not have AD pathology or have other dementing disorders. Markers that change with disease progression may offer utility in assessing the rates of disease progression and the efficacy of potential therapeutic agents on AD pathology. For both of these purposes, CSF Abeta42, amyloid imaging, and CSF tau appear to be very good markers of the presence of AD pathology as well as predictive of who will progress from MCI to AD. Volumetric MRI is also good at separating individuals with MCI and AD from controls and is predictive of who will progress from MCI to AD. Perhaps the most important role biomarkers will have, and the most needed at this time, lies in the identification of individuals who are cognitively normal, and yet have evidence of AD pathology (i.e. preclinical AD). Such individuals, it appears, can be identified with CSF Abeta42, amyloid imaging, and CSF tau. Such individuals are the most likely to benefit from future disease modifying/prevention therapies as they become available, and therefore represent the population in which the field can make the biggest therapeutic impact.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Tarawneh R,Holtzman DMdoi
10.1016/j.neuropharm.2010.04.006subject
Has Abstractpub_date
2010-09-01 00:00:00pages
310-22issue
4-5eissn
0028-3908issn
1873-7064pii
S0028-3908(10)00108-5journal_volume
59pub_type
杂志文章,评审abstract::Activation of the kappa opioid receptor (KOR) system mediates negative emotional states and considerable evidence suggests that KOR and their natural ligand, dynorphin, are involved in ethanol dependence and reward. The central amygdala (CeA) plays a major role in alcohol dependence and reinforcement. Dynorphin peptid...
journal_title:Neuropharmacology
pub_type: 杂志文章
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abstract::The properties of central ATP-mediated synaptic currents were studied using whole-cell patch-clamp recording in rat medial habenula slices. Release was shown to be calcium dependent with a Hill coefficient of approximately 2. The voltage dependence of synaptic current amplitudes was approximately linear. Some reductio...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(97)00127-5
更新日期:1997-09-01 00:00:00
abstract::The mGluR-mediated EPSP at parallel fibre-Purkinje cell synapses in the cerebellum was blocked concentration-dependently and reversibly by antagonists acting selectively on group-I mGluRs but not by an inhibitor of group-III receptors. The results provide pharmacological evidence that the receptor type responsible for...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(97)00014-2
更新日期:1997-03-01 00:00:00
abstract::The weaver defect results in a loss of baclofen- and adenosine-gated K+ conductance in the hippocampus of adult homozygous (wv/wv) mice. In addition, suppression of hippocampal epileptiform activity by baclofen is impaired (Jarolimek, W., Bäurle, J., Misgeld, U., 1998. Pore mutation in a G protein-gated inwardly recti...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(99)00089-1
更新日期:2000-01-04 00:00:00
abstract::The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mechanistic target of rapamycin (mTOR) signaling pathway has been associated with several pathologies in the central nervous system (CNS), including epilepsy. There is evidence supporting the hypothesis that the PI3Kγ signaling pathway may mediate the...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108156
更新日期:2020-10-01 00:00:00
abstract::An infusion of dopamine for 13 days into the nucleus accumbens of rat caused biphasic peaks of hyperactivity responding during infusion and an enhanced locomotor responsiveness to the dopamine agonist (-)N-n-propylnorapomorphine [(-)NPA] after the infusion when rats where initially preselected as low activity responde...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(85)90073-5
更新日期:1985-03-01 00:00:00
abstract::Glutamate may be a key transmitter in the emetic reflex arc. The present investigation focussed on the involvement of the NMDA subtype of glutamate receptors in cisplatin-induced emesis. Ferrets were injected with cisplatin (10 mg/kg i.v.) and either of the non-competitive NMDA receptor antagonists dextromethorphan or...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(96)00008-1
更新日期:1996-04-01 00:00:00
abstract::Selective serotonin (5-HT) re-uptake inhibitors (SSRIs) are commonly used in the treatment of generalized anxiety disorder in Humans. However, because only few animal models display overt anxious-like behavior, detailed preclinical studies of the anxiolytic properties of antidepressants are still lacking. Here, we stu...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.02.009
更新日期:2011-09-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)00151-h
更新日期:1995-02-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2019.03.014
更新日期:2020-06-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(96)00094-9
更新日期:1996-01-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.09.032
更新日期:2016-02-01 00:00:00
abstract::The effects of various benzodiazepine receptor ligands on the GABA autoreceptor have been studied in slices of cerebral cortex of the rat. The GABAA receptor agonist muscimol inhibited the K+-stimulated release of [3H]GABA with a pIC25 of 7.65 +/- 0.11. This effect was antagonised by the GABAA receptor antagonist bicu...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90059-7
更新日期:1988-10-01 00:00:00
abstract::The heart rate of the anaesthetized rabbit was slowed by electrical stimulation of the hypothalamus with 7-9 sec trains of 250-330 microA pulses, duration 1 msec, frequency 60 Hz. This vagally-mediated cardio-decelerator response was attenuated in a dose-dependent manner after intravenous administration of phenoxybenz...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(83)90258-7
更新日期:1983-01-01 00:00:00
abstract::Evidence indicates that angiotensin II type 2 receptors (AT2R) exert cerebroprotective actions during stroke. A selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exert beneficial effects in models of cardiac and renal disease, as well as hemorrhagic stroke. Here, we hypothesize that C21 may exer...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.01.044
更新日期:2014-06-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.11.025
更新日期:2016-03-01 00:00:00
abstract::Hippocampal volume reductions and functional impairments are reliable findings in posttraumatic stress disorder (PTSD) imaging studies. However, it is not clear if and how hippocampal dysfunction contributes to the etiology and maintenance of PTSD. Individuals with PTSD are often described as showing fear responses to...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2011.04.029
更新日期:2012-02-01 00:00:00
abstract::The role of the stress-induced increase in the uptake of tryptophan in brain in opioid-induced analgesia was investigated by modifying the uptake of amino acid in brain with injections of competing amino acids. Blockade of analgesia by valine (200 mg/kg, i.p.) alone, and by valine and tyrosine (100 mg/kg, i.p.), but n...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(85)90185-6
更新日期:1985-11-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
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更新日期:2000-07-10 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.06.016
更新日期:2012-01-01 00:00:00
abstract::The effects of intracerebroventricular administration of morphine, the selective mu-agonist DAMGO, the delta-agonist DPDPE, the kappa-preferring peptide dynorphin A(1-13) and the kappa-agonist U50,488H on locomotor behaviour in the guinea pig were investigated. Morphine (total dose = 0.01, 0.1, 1, 10, 200 nmol), DAMGO...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(92)90118-9
更新日期:1992-09-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2019.107735
更新日期:2020-05-01 00:00:00
abstract::Marijuana use in adolescence, but not adulthood, may permanently impair cognitive functioning and increase the risk of developing schizophrenia. Cortical oscillations are patterns of neural network activity implicated in cognitive processing, and are abnormal in patients with schizophrenia. We have recently reported t...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.07.006
更新日期:2014-11-01 00:00:00
abstract::The effects of microiontophoretically-applied and pneumatically-applied morphine on the spontaneous discharge of Purkinje cells in the cerebellum of the anesthetized cat were examined. Microiontophoretic application of morphine produced both inhibitory and excitatory responses of the Purkinje cells. Pneumatic applicat...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(89)90098-1
更新日期:1989-03-01 00:00:00
abstract::Mechanisms underlying the neuroprotective properties of the weak MAO-A inhibitor moclobemide are not understood. Increasing evidence suggests that a moderate increase in intracellular free protons may contribute to neuroprotective properties due to a proton-mediated decrease in neuronal activity. Therefore, we studied...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(00)00033-2
更新日期:2000-08-23 00:00:00
abstract::The effect of N-methyl-D-aspartate (NMDA) and L-glutamate on the concentration of intracellular free calcium (Cai) and on uptake of the calcium was determined in microsacs and synaptosomes isolated from mouse brain. L-Glutamate and NMDA increased Cai in hippocampal microsacs but had little or no effect on Cai in micro...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(91)90071-i
更新日期:1991-06-01 00:00:00
abstract::The active principle of marijuana, Delta9-tetrahydrocannabinol (Delta9-THC), exerts its pharmacological effects by binding to selective receptors present on the membranes of neurons and other cells. These cannabinoid receptors are normally engaged by a family of lipid mediators, called endocannabinoids, which are thou...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2004.07.018
更新日期:2004-01-01 00:00:00
abstract::Purine nucleotides, such as ATP and ADP, activate ionotropic P2X and metabotropic P2Y receptors to regulate neurotransmitter release in the peripheral as well as central nervous system. Here we report another type of ATP-induced presynaptic modulation of glutamate release in rat medullary dorsal horn neurons. Glutamat...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.01.020
更新日期:2015-06-01 00:00:00
abstract::Epidemiological studies have reported that cigarette smoking may protect from neurodegenerative diseases such as Parkinson's disease. These protective effects are thought to be mediated by nicotine. Recent data showed that nicotine significantly decreases respiratory control ratio (RCR) and superoxide anion generation...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(03)00041-8
更新日期:2003-04-01 00:00:00
abstract::The mechanisms underlying the neuroprotective effects of cannabidiol (CBD) were studied in vivo using a hypoxic-ischemic (HI) brain injury model in newborn pigs. One- to two-day-old piglets were exposed to HI for 30 min by interrupting carotid blood flow and reducing the fraction of inspired oxygen to 10%. Thirty minu...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.03.027
更新日期:2013-08-01 00:00:00