Fluid Biomarkers in Clinical Trials of Alzheimer's Disease Therapeutics.

Abstract:

:With the demographic shift of the global population toward longer life expectancy, the number of people living with Alzheimer's disease (AD) has rapidly expanded and is projected to triple by the year 2050. Current treatments provide symptomatic relief but do not affect the underlying pathology of the disease. Therapies that prevent or slow the progression of the disease are urgently needed to avoid this growing public health emergency. Insights gained from decades of research have begun to unlock the pathophysiology of this complex disease and have provided targets for disease-modifying therapies. In the last decade, few therapeutic agents designed to modify the underlying disease process have progressed to clinical trials and none have been brought to market. With the focus on disease modification, biomarkers promise to play an increasingly important role in clinical trials. Six biomarkers have now been included in diagnostic criteria for AD and are regularly incorporated into clinical trials. Three biomarkers are neuroimaging measures - hippocampal atrophy measured by magnetic resonance imaging (MRI), amyloid uptake as measured by Pittsburg compound B positron emission tomography (PiB-PET), and decreased fluorodeoxyglucose (18F) uptake as measured by PET (FDG-PET) - and three are sampled from fluid sources - cerebrospinal fluid levels of amyloid β42 (Aβ42), total tau, and phosphorylated tau. Fluid biomarkers are important because they can provide information regarding the underlying biochemical processes that are occurring in the brain. The purpose of this paper is to review the literature regarding the existing and emerging fluid biomarkers and to examine how fluid biomarkers have been incorporated into clinical trials.

journal_name

Front Neurol

journal_title

Frontiers in neurology

authors

Ritter A,Cummings J

doi

10.3389/fneur.2015.00186

subject

Has Abstract

pub_date

2015-08-31 00:00:00

pages

186

issn

1664-2295

journal_volume

6

pub_type

杂志文章,评审
  • Spontaneous Intracerebral Hemorrhage Due to Delta Storage Pool Disease in a Patient on a Serotonin-Norepinephrine Reuptake Inhibitor.

    abstract::We report a case of spontaneous intracerebral hemorrhage (sICH) due to delta storage pool disease in a 60-year-old female on a serotonin-norepinephrine reuptake inhibitor (SNRI). Increased susceptibility to SNRI-effects on hemostasis was due to a genetic disposition mediated by a polymorphism of the SLC6A4 gene coding...

    journal_title:Frontiers in neurology

    pub_type:

    doi:10.3389/fneur.2019.01257

    authors: Leibetseder A,Wagner J,Tomasits J,Haring HP,Hutterer M,Trenkler J,von Oertzen TJ

    更新日期:2019-11-26 00:00:00

  • Coding of Velocity Storage in the Vestibular Nuclei.

    abstract::Semicircular canal afferents sense angular acceleration and output angular velocity with a short time constant of ≈4.5 s. This output is prolonged by a central integrative network, velocity storage that lengthens the time constants of eye velocity. This mechanism utilizes canal, otolith, and visual (optokinetic) infor...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2017.00386

    authors: Yakushin SB,Raphan T,Cohen B

    更新日期:2017-08-16 00:00:00

  • A New Questionnaire for Estimating the Severity of Visual Height Intolerance and Acrophobia by a Metric Interval Scale.

    abstract:AIMS:To construct and validate a short scale for the assessment of the severity of visual height intolerance (vHI) and acrophobia. METHODS:The questionnaire was developed from two earlier representative epidemiological studies (n = 5,529). Items were applied in a telephone survey of a representative population-based s...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2017.00211

    authors: Huppert D,Grill E,Brandt T

    更新日期:2017-06-01 00:00:00

  • Sleep loss in resident physicians: the cause of medical errors?

    abstract::This review begins with the history of the events starting with the death of Libby Zion that lead to the Bell Commission, that the studied her death and made recommendations for improvement that were codified into law in New York state as the 405 law that the ACGME essentially adopted in putting a cap on work hours an...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2010.00128

    authors: Kramer M

    更新日期:2010-10-20 00:00:00

  • Imaging Mild Cognitive Impairment and Dementia in Parkinson's Disease.

    abstract::Cognitive dysfunction is a significant non-motor feature of Parkinson's disease, with the risk of dementia increasing with prolonged disease duration. Multiple cognitive domains are affected, and the pathophysiology cannot be explained by dopaminergic loss alone. Sophisticated neuroimaging techniques can detect the na...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章,评审

    doi:10.3389/fneur.2020.00047

    authors: Sasikumar S,Strafella AP

    更新日期:2020-01-31 00:00:00

  • Vagus Nerve Stimulation Attenuates Cerebral Microinfarct and Colitis-induced Cerebral Microinfarct Aggravation in Mice.

    abstract::Cerebral cortical microinfarct (CMI) is common in patients with dementia and cognitive decline. Emerging studies reported that intestinal dysfunction influenced the outcome of ischemic stroke and that vagus nerve stimulation (VNS) protected against ischemic stroke. However, the effects of intestinal dysfunction and VN...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2018.00798

    authors: Chen X,He X,Luo S,Feng Y,Liang F,Shi T,Huang R,Pei Z,Li Z

    更新日期:2018-09-26 00:00:00

  • A Comprehensive Analysis of 2013 Dystrophinopathies in China: A Report From National Rare Disease Center.

    abstract::Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive neuromuscular disorders caused by mutations in DMD. A high-quality database of DMD/BMD is essential not only for clinical practice but also for fundamental research. Here, we aimed to build the largest Chinese national dystrop...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2020.572006

    authors: Tong YR,Geng C,Guan YZ,Zhao YH,Ren HT,Yao FX,Ling C,Wang DC,Chen L,Cui LY,Zhang SY,Dai Y

    更新日期:2020-09-30 00:00:00

  • Vision and Vision-Related Measures in Progressive Multiple Sclerosis.

    abstract::Background: Over the last few years there has been growing interest in use of visual measures as useful tools for multiple sclerosis (MS) prognosis and tracking. Optic neuritis (ON) being a prevalent and often-presenting symptom of the disease, as well as the high occurrence rate of posterior visual system damage inde...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2019.00455

    authors: Backner Y,Petrou P,Glick-Shames H,Raz N,Zimmermann H,Jost R,Scheel M,Paul F,Karussis D,Levin N

    更新日期:2019-05-03 00:00:00

  • Prospective Follow-up of Intramedullary Slitlike Cavities: A Consecutive Series of 48 Patients.

    abstract::Object: Predicting whether intramedullary slitlike cavity (SC) will worsen over time or remain stable is an outstanding clinical challenge. The aim of this study was to identify early features of SC (clinical and magnetic resonance imaging [MRI] findings). Methods: We prospectively included all patients referred to ou...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2020.00495

    authors: Faillot M,Morar S,Delphine S,El-Mendili M,Ducreux D,Parker F,Aghakhani N

    更新日期:2020-06-12 00:00:00

  • Cochlear Implantation of Bilaterally Deafened Patients with Tinnitus Induces Sustained Decrease of Tinnitus-Related Distress.

    abstract:OBJECTIVE:Tinnitus is a common symptom of hearing impairment. Patients who are bilaterally hard of hearing are often affected by tinnitus. However, they cannot undergo any of the standard tinnitus therapies, since they rely on hearing. Cochlear implantation (CI) used to treat severe hearing disabilities, such as bilate...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2017.00158

    authors: Knopke S,Szczepek AJ,Häussler SM,Gräbel S,Olze H

    更新日期:2017-04-25 00:00:00

  • Three Cases of Hemiconvulsion-Hemiplegia-Epilepsy Syndrome With Focal Cortical Dysplasia Type IIId.

    abstract::Hemiconvulsion-hemiplegia-epilepsy syndrome (HHES) is a subset of acute encephalopathy characterized by infantile-onset with acute hemiconvulsive febrile status and subsequent unilateral cerebral atrophy and hemiparesis. In the chronic phase, patients with HHES develop epilepsy, typically displayed as intractable foca...

    journal_title:Frontiers in neurology

    pub_type:

    doi:10.3389/fneur.2019.01233

    authors: Itamura S,Okanishi T,Arai Y,Nishimura M,Baba S,Ichikawa N,Hirayama Y,Ishihara N,Hiraide T,Ishigaki H,Fukuda T,Otsuki Y,Enoki H,Fujimoto A

    更新日期:2019-11-20 00:00:00

  • Amplitudes of Pain-Related Evoked Potentials Are Useful to Detect Small Fiber Involvement in Painful Mixed Fiber Neuropathies in Addition to Quantitative Sensory Testing - An Electrophysiological Study.

    abstract::To investigate the usefulness of pain-related evoked potentials (PREP) elicited by electrical stimulation for the identification of small fiber involvement in patients with mixed fiber neuropathy (MFN). Eleven MFN patients with clinical signs of large fiber impairment and neuropathic pain and ten healthy controls unde...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2015.00244

    authors: Hansen N,Kahn AK,Zeller D,Katsarava Z,Sommer C,Üçeyler N

    更新日期:2015-12-07 00:00:00

  • Cerebral Microcirculation and Histological Mapping After Severe Head Injury: A Contusion and Acceleration Experimental Model.

    abstract:Background:Cerebral microcirculation after severe head injury is heterogeneous and temporally variable. Microcirculation is dependent upon the severity of injury, and it is unclear how histology relates to cerebral regional blood flow. Objective:This study assesses the changes of cerebral microcirculation blood flow o...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2018.00277

    authors: Bellapart J,Cuthbertson K,Dunster K,Diab S,Platts DG,Raffel OC,Gabrielian L,Barnett A,Paratz J,Boots R,Fraser JF

    更新日期:2018-05-07 00:00:00

  • Hereditary Spastic Paraplegia and Intellectual Disability: Clinicogenetic Lessons From a Family Suggesting a Dual Genetics Diagnosis.

    abstract::Hereditary spastic paraplegias (HSPs) are a heterogeneous group of genetic disorders with spastic paraparesis as the main clinical feature. Complex forms may co-occur with other motor, sensory, and cognitive impairment. A growing number of loci and genes are being identified, but still more than 50% of the patients re...

    journal_title:Frontiers in neurology

    pub_type:

    doi:10.3389/fneur.2020.00041

    authors: Aguilera-Albesa S,de la Hoz AB,Ibarluzea N,Ordóñez-Castillo AR,Busto-Crespo O,Villate O,Ibiricu-Yanguas MA,Yoldi-Petri ME,García de Gurtubay I,Perez de Nanclares G,Pereda A,Tejada MI

    更新日期:2020-02-14 00:00:00

  • Initial Response to Antiepileptic Drugs in Patients with Newly Diagnosed Epilepsy As a Predictor of Long-term Outcome.

    abstract:Objective:To investigate the correlation between initial response to antiepileptic drugs (AEDs) and long-term outcomes after 3 years in patients with newly diagnosed epilepsy. Methods:This prospective study included 204 patients with newly diagnosed epilepsy, who were followed-up for at least 36 months. The long-term ...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2017.00658

    authors: Xia L,Ou S,Pan S

    更新日期:2017-12-08 00:00:00

  • Temporal Dynamics of Diffusion Metrics in Early Multiple Sclerosis and Clinically Isolated Syndrome: A 2-Year Follow-Up Tract-Based Spatial Statistics Study.

    abstract::Background: Tract-based spatial statistics (TBSS) is suitable for the assessment of voxel-wise changes in fiber integrity in WM tracts in the entire brain. Longitudinal TBSS analyses of early multiple sclerosis (MS) using 3 Tesla magnetic resonance imaging (MRI) are not common. Objective: To characterize microstructur...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2019.01165

    authors: Schneider R,Genç E,Ahlborn C,Gold R,Lukas C,Bellenberg B

    更新日期:2019-11-05 00:00:00

  • Microbial Neuraminidase Induces a Moderate and Transient Myelin Vacuolation Independent of Complement System Activation.

    abstract:AIMS:Some central nervous system pathogens express neuraminidase (NA) on their surfaces. In the rat brain, a single intracerebroventricular (ICV) injection of NA induces myelin vacuolation in axonal tracts. Here, we explore the nature, the time course, and the role of the complement system in this damage. METHODS:The ...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2017.00078

    authors: Granados-Durán P,López-Ávalos MD,Cifuentes M,Pérez-Martín M,Fernández-Arjona MD,Hughes TR,Johnson K,Morgan BP,Fernández-Llebrez P,Grondona JM

    更新日期:2017-03-07 00:00:00

  • Epilepsy and Its Interaction With Sleep and Circadian Rhythm.

    abstract::Growing evidence shows the bidirectional interactions between sleep, circadian rhythm, and epilepsy. Comprehending how these interact with each other may help to advance our understanding of the pathophysiology of epilepsy and develop new treatment strategies to improve seizure control by reducing the medication side ...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章,评审

    doi:10.3389/fneur.2020.00327

    authors: Jin B,Aung T,Geng Y,Wang S

    更新日期:2020-05-08 00:00:00

  • Optical Coherence Tomography in Patients with Chronic Migraine: Literature Review and Update.

    abstract::Migraine is a chronic disease characterized by unilateral, pulsating, and often moderate-to-severe recurrent episodes of headache with nausea and vomiting. It affects approximately 15% of the general population, yet the underlying pathophysiological mechanisms are not fully understood. Optical coherence tomography (OC...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章,评审

    doi:10.3389/fneur.2017.00684

    authors: Ascaso FJ,Marco S,Mateo J,Martínez M,Esteban O,Grzybowski A

    更新日期:2017-12-13 00:00:00

  • Hemorrhagic Transformation in Ischemic Moyamoya Disease: Clinical Characteristics, Radiological Features, and Outcomes.

    abstract::Objective: Hemorrhagic transformation (HT) in ischemic moyamoya disease (MMD), reasonably defined as hemorrhage events in patients with ischemic onset manifestation, leads to a poor outcome. This study aims to reveal factors associated with HT in patients with ischemic onset manifestation and to assess the outcome of ...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2020.00517

    authors: Lu J,Li Z,Zhao Y,Chen X,Shi G,Zhao J

    更新日期:2020-06-25 00:00:00

  • Reconsidering the role of neuronal intrinsic properties and neuromodulation in vestibular homeostasis.

    abstract::The sensorimotor transformations performed by central vestibular neurons constantly adapt as the animal faces conflicting sensory information or sustains injuries. To ensure the homeostasis of vestibular-related functions, neural changes could in part rely on the regulation of 2° VN intrinsic properties. Here we revie...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2012.00025

    authors: Beraneck M,Idoux E

    更新日期:2012-02-28 00:00:00

  • Excessive Daytime Sleepiness in Tension-Type Headache: A Population Study.

    abstract::Excessive daytime sleepiness (EDS) is a prevalent sleep-related complaint across the general population and has been reported to be associated with headache. Tension-type headache (TTH) is the most commonly encountered headache and accounts for a significant amount of disease burden. However, the association between E...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2019.01282

    authors: Kim KM,Kim J,Cho SJ,Kim WJ,Yang KI,Yun CH,Chu MK

    更新日期:2019-12-03 00:00:00

  • Alpha-Synuclein: From Early Synaptic Dysfunction to Neurodegeneration.

    abstract::Over the last two decades, many experimental and clinical studies have provided solid evidence that alpha-synuclein (α-syn), a small, natively unfolded protein, is closely related to Parkinson's disease (PD) pathology. To provide an overview on the different roles of this protein, here we propose a synopsis of seminal...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章,评审

    doi:10.3389/fneur.2018.00295

    authors: Ghiglieri V,Calabrese V,Calabresi P

    更新日期:2018-05-04 00:00:00

  • Consecutive Slides on Axial View Is More Effective Than Transversal Diameter to Differentiate Mechanisms of Single Subcortical Infarctions in the Lenticulostriate Artery Territory.

    abstract::Objective: Lipohyalinosis or atherosclerosis might be responsible for single subcortical infarctions (SSIs); however, ways of differentiating between the two clinically remain uncertain. We aimed to investigate whether consecutive slides on axial view or transversal diameter is more effective to differentiate mechanis...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2019.00336

    authors: Cao Y,Zhang M,Zhou L,Yao M,Peng B,Zhu Y,Ni J,Cui L

    更新日期:2019-04-09 00:00:00

  • Parkinson's Disease Caregiver Strain in Singapore.

    abstract::Background: Caregiver strain is recognized globally with Parkinson's disease (PD). Comparatively little is understood about caregiver burden and strain in Asia. Objective: To investigate caregiver strain for families living with PD in Singapore, in light of international data. Methods: Ninety-four caregivers were recr...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2020.00455

    authors: Tan SB,Williams AF,Tan EK,Clark RB,Morris ME

    更新日期:2020-06-23 00:00:00

  • Motor Nerve Conduction Tests in Carpal Tunnel Syndrome.

    abstract::Background: For the preoperatively often required confirmation of clinically defined carpal tunnel syndrome (CTS), sensory as well as motor nerve conduction studies can be applied. The aim of this study was to test the sensitivity of specific motor nerve conduction tests in comparison with, as well as in addition to, ...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2019.00149

    authors: Kasius KM,Claes F,Verhagen WIM,Meulstee J

    更新日期:2019-03-14 00:00:00

  • Glucocerebrosidase involvement in Parkinson disease and other synucleinopathies.

    abstract::Mutations in both copies (homozygous or compound heterozygous) of the gene encoding the lysosomal enzyme glucocerebrosidase, which cleaves the glycolipid glucocerebroside into glucose and ceramide cause Gaucher disease. However, multiple independent studies have also reported an association between GBA mutations and P...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2012.00065

    authors: Almeida Mdo R

    更新日期:2012-04-27 00:00:00

  • Muscular Activity Modulation During Post-operative Walking With Hybrid Assistive Limb (HAL) in a Patient With Thoracic Myelopathy Due to Ossification of Posterior Longitudinal Ligament: A Case Report.

    abstract::Disorders of the central nervous system sometimes cause severe sensory motor paralysis accompanied by gait impairment. Recently, there are several reports on the effectiveness of robot-assisted gait training for patients experiencing these issues. The purpose of this case report was to assess the neuromechanical effec...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2020.00102

    authors: Kadone H,Kubota S,Abe T,Noguchi H,Miura K,Koda M,Shimizu Y,Hada Y,Sankai Y,Suzuki K,Yamazaki M

    更新日期:2020-03-31 00:00:00

  • Brain Structural and Functional Imaging Findings in Medication-Overuse Headache.

    abstract::This chapter overviews research neuroimaging findings of patients with medication-overuse headache (MOH). Results indicate; (i) correlations between neuropathology and medication-overuse; (ii) changes in brain morphology and cortical function; and (iii) brain recovery subsequent to withdrawal of medication that was ov...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章,评审

    doi:10.3389/fneur.2019.01336

    authors: Chong CD

    更新日期:2020-01-28 00:00:00

  • Cognitive Processing Impacts High Frequency Intracranial EEG Activity of Human Hippocampus in Patients With Pharmacoresistant Focal Epilepsy.

    abstract::The electrophysiological EEG features such as high frequency oscillations, spikes and functional connectivity are often used for delineation of epileptogenic tissue and study of the normal function of the brain. The epileptogenic activity is also known to be suppressed by cognitive processing. However, differences bet...

    journal_title:Frontiers in neurology

    pub_type: 杂志文章

    doi:10.3389/fneur.2020.578571

    authors: Cimbalnik J,Pail M,Klimes P,Travnicek V,Roman R,Vajcner A,Brazdil M

    更新日期:2020-10-27 00:00:00