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Biomarkers and Alzheimer's

Lisa Mosconi, Aneela Rahman, Ivan Diaz, Xian Wu, Olivia Scheyer, Hollie Webb Hristov, Shankar Vallabhajosula, Richard S Isaacson, Mony J de Leon, Roberta Diaz Brinton
Two thirds of all persons with late-onset Alzheimer's disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer's disease (AD) biomarker changes [brain β-amyloid load via 11C-PiB PET, and neurodegeneration via 18F-FDG PET and structural MRI] and cognitive performance in midlife...
2018: PloS One
Pete Heinzelman, David N Powers, James A Wohlschlegel, Varghese John
Analyses of bloodborne nanoscale extracellular vesicles (nsEVs) have shown tremendous promise in enabling the development of noninvasive blood-based clinical diagnostic tests, predicting and monitoring the efficacy of treatment programs, and identifying new drug targets in the context of health conditions such as cancer and Alzheimer's disease. In this chapter we present a protocol for generating global nsEV proteomic profiles that can further the utility of nsEV analysis for the above biomedical applications by enlightening us of differences in protein abundance across normal and disease state nsEVs...
2019: Methods in Molecular Biology
Xiao-Hong Zhu, Wei Chen
Brain relies on glucose and oxygen metabolisms to generate biochemical energy in the form of adenosine triphosphate (ATP) for supporting electrophysiological activities and neural signaling under resting or working state. Aging is associated with declined mitochondrial functionality and decreased cerebral energy metabolism, and thus, is a major risk factor in developing neurodegenerative diseases including Alzheimer's disease (AD). However, there is an unmet need in the development of novel neuroimaging tools and sensitive biomarkers for detecting abnormal energy metabolism and impaired mitochondrial function, especially in an early stage of the neurodegenerative diseases...
2018: Frontiers in Aging Neuroscience
Ann D Cohen, Susan M Landau, Beth E Snitz, William E Klunk, Kaj Blennow, Henrik Zetterberg
Alzheimer's disease (AD) is characterized by amyloid plaques and tau pathology (neurofibrillary tangles and neuropil threads). Amyloid plaques are primarily composed of aggregated and oligomeric β-amyloid (Aβ) peptides ending at position 42 (Aβ42). The development of fluid and PET biomarkers for Alzheimer's disease (AD), has allowed for detection of Aβ pathology in vivo and marks a major advancement in understanding the role of Aβ in Alzheimer's disease (AD). In the recent National Institute on Aging and Alzheimer's Association (NIA-AA) Research Framework, AD is defined by the underlying pathology as measured in patients during life by biomarkers (Jack et al...
December 8, 2018: Molecular and Cellular Neurosciences
Michael S Rafii
Alzheimer's disease (AD) pathology and early-onset dementia develop almost universally in Down syndrome (DS). AD is defined neuropathologically by the presence of extracellular plaques of aggregated amyloid β protein and intracellular neurofibrillary tangles (NFTs) of aggregated hyperphosphorylated tau protein. The development of radiolabeled positron emission tomography (PET) ligands for amyloid plaques and tau tangles enables the longitudinal assessment of the spatial pattern of their accumulation in relation to symptomatology...
December 8, 2018: Developmental Neurobiology
Fatemeh Ahmadi-Motamayel, Mohammad Taghi Goodarzi, Shabnam Tarazi, Mehrangiz Vahabian
AIM: The aim of this study was to evaluate acetylcholinesterase (AChE) and pseudocholinesterase (PChE) in whole saliva in patients with Alzheimer's disease (AD) and in healthy subjects. Saliva has a high potential for keeping track of general health and diseases. AD is a type of dementia with reduction in brain cholinergic markers that causes memory, thinking, and behavior problems. Up to 90% decrease in AChE activity has been observed in AD. METHODS AND RESULTS: Thirty healthy subjects and 30 patients with AD participated in this study...
December 11, 2018: Special Care in Dentistry
Bridget Martinez, Philip V Peplow
Alzheimer's disease (AD) is the most common age-related, progressive neurodegenerative disease. It is characterized by memory loss and cognitive decline and responsible for most cases of dementia in the elderly. Late-onset or sporadic AD accounts for > 95% of cases, with age at onset > 65 years. Currently there are no drugs or other therapeutic agents available to prevent or delay the progression of AD. The cellular and molecular changes occurring in the brains of individuals with AD include accumulation of β-amyloid peptide and hyperphosphorylated tau protein, decrease of acetylcholine neurotransmitter, inflammation, and oxidative stress...
February 2019: Neural Regeneration Research
Eduardo Torrealba, Pilar Garcia-Morales, Juan Carlos Cejudo, Mario Diaz, Francisco Rodriguez-Esparragon, Oscar Fabre, Fatima Mesa-Herrera, Raquel Marin, Florentino Sanchez-Garcia, Aurelio Rodriguez-Perez, Nina Gramunt
BACKGROUND: Assessment of hippocampal amnesia is helpful to distinguish between normal cognition and mild cognitive impairment (MCI), but not for identifying converters to dementia. Here biomarkers are useful but novel neuropsychological approaches are needed in their absence. The In-out-test assesses episodic memory using a new paradigm hypothesized to avoid reliance on executive function, which may compensate for damaged memory networks. OBJECTIVE: To assess the validity of the In-out-test in identifying prodromal Alzheimer's disease (PAD) in a clinical setting, by comparing this to the Free and Cued Selective Reminding Test (FCSRT) and cerebrospinal fluid biomarkers...
December 3, 2018: Journal of Alzheimer's Disease: JAD
Pengbo Jiang, Xuetong Wang, Qiongling Li, Leiming Jin, Shuyu Li
Alzheimer's Disease (AD), as a severe neurodegenerative disease, is now attracting more and more researchers' attention in the healthcare. With the development of Magnetic Resonance Imaging (MRI), the neuroimaging-based longitudinal analysis is gradually becoming an important research direction to understand and trace the process of the AD. And regression analysis has been commonly adopted in the AD pattern analysis and progression prediction. However, most existing methods assume that all input features are equally related to the output variables, which ignore the difference in terms of the correlation...
December 6, 2018: IEEE Journal of Biomedical and Health Informatics
Aurélie Bussy, B Joy Snider, Dean Coble, Chengjie Xiong, Anne M Fagan, Carlos Cruchaga, Tammie L S Benzinger, Brian A Gordon, Jason Hassenstab, Randall J Bateman, John C Morris
The apolipoprotein E ε4 allele (APOE4) is the major genetic risk factor for sporadic Alzheimer's disease (AD). APOE4 may have effects on cognition and brain atrophy years before the onset of symptomatic AD. We analyzed the effects of APOE4 in a unique cohort of young adults who had undergone comprehensive assessments as part of the Dominantly Inherited Alzheimer Network (DIAN), an international longitudinal study of individuals from families with autosomal dominant AD. We analyzed the effect of an APOE4 allele on cognitive measures, volumetric MRI, amyloid deposition, glucose metabolism, and on cerebrospinal fluid levels of AD biomarkers in 162 participants that did not carry the mutant gene (noncarriers)...
October 13, 2018: Neurobiology of Aging
Ewa Laskowska, Dorota Kuczyńska-Wiśnik, Barbara Lipińska
Protein homeostasis (proteostasis) refers to the ability of cells to preserve the correct balance between protein synthesis, folding and degradation. Proteostasis is essential for optimal cell growth and survival under stressful conditions. Various extracellular and intracellular stresses including heat shock, oxidative stress, proteasome malfunction, mutations and aging-related modifications can result in disturbed proteostasis manifested by enhanced misfolding and aggregation of proteins. To limit protein misfolding and aggregation cells have evolved various strategies including molecular chaperones, proteasome system and autophagy...
December 6, 2018: Journal of Proteomics
Claire Cury, Stanley Durrleman, David M Cash, Marco Lorenzi, Jennifer M Nicholas, Martina Bocchetta, John C van Swieten, Barbara Borroni, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, James B Rowe, Caroline Graff, Fabrizio Tagliavini, Giovanni B Frisoni, Robert Laforce, Elizabeth Finger, Alexandre de Mendonça, Sandro Sorbi, Sebastien Ourselin, Jonathan D Rohrer, Marc Modat
Brain atrophy as measured from structural MR images, is one of the primary imaging biomarkers used to track neurodegenerative disease progression. In diseases such as frontotemporal dementia or Alzheimer's disease, atrophy can be observed in key brain structures years before any clinical symptoms are present. Atrophy is most commonly captured as volume change of key structures and the shape changes of these structures are typically not analysed despite being potentially more sensitive than summary volume statistics over the entire structure...
December 6, 2018: NeuroImage
Annika Öhrfelt, Ann Brinkmalm, Julien Dumurgier, Henrik Zetterberg, Elodie Bouaziz-Amar, Jacques Hugon, Claire Paquet, Kaj Blennow
Synaptic degeneration is central in Alzheimer's disease (AD) pathogenesis and biomarkers to monitor this pathophysiology in living patients are warranted. We developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) for the measurement of the pre-synaptic protein SNAP-25 in cerebrospinal fluid (CSF) and evaluated it as a biomarker for AD. CSF samples included a pilot study consisting of AD (N=26) and controls (N=26), and two independent clinical cohorts of AD patients and controls. Cohort I included CSF samples from patients with dementia due to AD (N=17), patients with mild cognitive impairment (MCI) due to AD (N=5) and controls (N=17), and cohort II CSF samples from patients with dementia due to AD (N=24), patients with MCI due to AD (N=18) and controls (N=36)...
December 4, 2018: Neuroscience
Hedieh Shahpasand-Kroner, Hans-W Klafki, Chris Bauer, Johannes Schuchhardt, Melanie Hüttenrauch, Martina Stazi, Caroline Bouter, Oliver Wirths, Jonathan Vogelgsang, Jens Wiltfang
BACKGROUND: The quantification of amyloid-beta (Aβ) peptides in blood plasma as potential biomarkers of Alzheimer's disease (AD) is hampered by very low Aβ concentrations and the presence of matrix components that may interfere with the measurements. METHODS: We developed a two-step immunoassay for the simultaneous measurement of the relative levels of Aβ38, Aβ40 and Aβ42 in human EDTA plasma. The assay was employed for the study of 23 patients with dementia of the Alzheimer's type (AD-D) and 17 patients with dementia due to other reasons (OD)...
December 8, 2018: Alzheimer's Research & Therapy
Åsa Sandelius, Nicholas C Cullen, Åsa Källén, Lars Rosengren, Crister Jensen, Vesna Kostanjevecki, Manu Vandijck, Henrik Zetterberg, Kaj Blennow
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers reflect ongoing processes in the brain. Growth-associated protein 43 (GAP-43) is highly upregulated in brain tissue shortly after experimental ischemia suggesting the CSF GAP-43 concentration may be altered in ischemic brain disorders. CSF GAP-43 concentration is elevated in Alzheimer's disease patients; however, patients suffering from stroke have not been studied previously. METHODS: The concentration of GAP-43 was measured in longitudinal CSF samples from 28 stroke patients prospectively collected on days 0-1, 2-4, 7-9, 3 weeks, and 3-5 months after ischemia and cross-sectionally in 19 controls...
December 7, 2018: BMC Neurology
Mohammad Golam Sabbir
Ca2+ /calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a serine/threonine kinase that is activated following an increase in the intracellular Ca2+ concentration and activates multiple signaling cascades that control physiologically important neuronal processes. CaMKK2 has been implicated in schizophrenia, bipolar disease, neurodegeneration, and cancer. Using isoelectric focusing (IEF) and mass spectrometry-based proteomic analysis, it was found that knockdown (KD) of CaMKK2 in cultured adult primary dorsal root ganglion (DRG) neurons resulted in the reduction of transferrin (TF) phosphorylation at multiple functionally relevant residues which corresponded to loss of an acidic fraction (pH~3-4) of TF...
2018: Frontiers in Molecular Biosciences
Qing Wang, Wenjun Zhou, Jie Zhang
Objective: Preclinical studies have found both hyperactivity of hypothalamic- pituitary- adrenal (HPA) axis and synaptic degeneration are involved in the pathogenesis of Alzheimer's disease (AD). However, the data on the relationship of activity of HPA axis and synaptic degeneration in humans are limited. Methods: We compared CSF cortisol levels in 310 subjects, including 92 cognitively normal older people, 149 patients with mild cognitive impairment (MCI), and 69 patients with mild AD. Several linear and logistic regression models were conducted to investigate associations between CSF cortisol and synaptosomal-associated protein 25 (SNAP-25, reflecting synaptic degeneration) and other AD-related biomarkers...
2018: Frontiers in Aging Neuroscience
Chelsea G Cox, Mary M Ryan B A, Daniel L Gillen, Joshua D Grill
OBJECTIVE: All Alzheimer disease (AD) clinical trials, including those enrolling patients with mild cognitive impairment (MCI), require dyadic participation. The purpose of this study was to elucidate how people with MCI and their study partners decide whether to enroll in clinical trials. METHODS: This was a mixed methods interview study. We interviewed patient participants with a consensus research diagnosis of MCI and their study partners. Interviews examined how dyads decide whether to enroll in a clinical trial and whether AD biomarker testing affects willingness to enroll...
November 3, 2018: American Journal of Geriatric Psychiatry
Prabha Siddarth, Alison C Burggren, David A Merrill, Linda M Ercoli, Zanjbeel Mahmood, Jorge R Barrio, Gary W Small
BACKGROUND: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with the apolipoprotein E (APOE) gene, has been implicated in Alzheimer's disease (AD). TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. While early reports indicated that the longer length poly-T allele of TOMM40 increases risk for AD, these findings have not been consistently replicated in further studies...
2018: PloS One
Stephen F Carter, Konstantinos Chiotis, Agneta Nordberg, Elena Rodriguez-Vieitez
PURPOSE: The spatial resolution of 18 F-fluorodeoxyglucose PET does not allow the specific cellular origin of its signal to be determined, but it is commonly accepted that transport and trapping of 18 F-fluorodeoxyglucose reflects neuronal glucose metabolism. The main frameworks for the diagnosis of Alzheimer's disease suggest that hypometabolism measured with 18 F-fluorodeoxyglucose PET is a biomarker of neuronal injury and neurodegeneration. There is preclinical evidence to suggest that astrocytes contribute, at least partially, to the in vivo 18 F-fluorodeoxyglucose PET signal...
December 4, 2018: European Journal of Nuclear Medicine and Molecular Imaging
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