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Biomarkers and Alzheimer's

Chen Chen, Xun Hou, Jinhai Si
We have designed a multi-analyte biosensing platform based on a hybrid whispering gallery mode resonator to detect protein biomarkers, e.g. those allowing the early diagnosis of Alzheimer's disease. Our proposed biosensor dependent on the hybrid mode naturally extends the capabilities of both plasmonic sensor and photonic sensor and thus performs better interrogation sensitivity. A multi-resonance of the hybrid mode could occur and the field intensity achieved its maximum value, thereby enabling a very strong light-matter interaction...
February 15, 2019: Nanotechnology
Joana R F Santos, Chris Bauer, Johannes Schuchhardt, Dirk Wedekind, Katharina Waniek, Ingolf Lachmann, Jens Wiltfang, Jonathan Vogelgsang
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques (senile plaques) and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein. This process leads to neuronal degradation and neuronal death. Phosphorylation of tau protein at threonine 231 (p-tau231) has been shown to be characteristic in post-mortem brain tissue of patients with AD and it can be sensitively detected in cerebrospinal fluid (CSF). Therefore, it may serve as a biomarker to support the diagnosis of AD...
February 14, 2019: Journal of Neural Transmission
Emily Joy Rogalski, Jaiashre Sridhar, Adam Martersteck, Benjamin Rader, Derin Cobia, Anupa K Arora, Angela J Fought, Eileen H Bigio, Sandra Weintraub, Marek-Marsel Mesulam, Alfred Rademaker
INTRODUCTION: Primary progressive aphasia (PPA) displays variable progression trajectories that require further elucidation. METHODS: Longitudinal quantitation of atrophy and language over 12 months was completed for PPA patients with and without positive amyloid PET (PPAAβ+ and PPAAβ- ), an imaging biomarker of underlying Alzheimer's disease. RESULTS: Over 12 months, both PPA groups showed significantly greater cortical atrophy rates in the left versus right hemisphere, with a more widespread pattern in PPAAβ+ ...
February 11, 2019: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Mingliang Wang, Daoqiang Zhang, Dinggang Shen, Mingxia Liu
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive impairment of memory and other cognitive functions. Currently, many multi-task learning approaches have been proposed to predict the disease progression at the early stage using longitudinal data, with each task corresponding to a particular time point. However, the underlying association among different time points in disease progression is still under-explored in previous studies. To this end, we propose a multi-task exclusive relationship learning model to automatically capture the intrinsic relationship among tasks at different time points for estimating clinical measures based on longitudinal imaging data...
January 30, 2019: Medical Image Analysis
Edin Begic, Suncica Hadzidedic, Ajla Kulaglic, Belma Ramic-Brkic, Zijo Begic, Mirsada Causevic
Alzheimer's disease represents the most common age-related neurodegenerative disorder and a leading cause of progressive cognitive impairment. Predicting cognitive decline is challenging but would be invaluable in an increasingly aging population which also experiences a rising cardiovascular risk. In order to examine whether plasma measurements of one of the established biomarkers of heart failure, brain natriuretic peptide (BNP), reflect a decline in cognitive function, associated with Alzheimer's disease neurodegeneration, BNP levels were analysed, by using a novel assay called a SOMAscan, in 1...
2019: PloS One
Garam Lee, Kwangsik Nho, Byungkon Kang, Kyung-Ah Sohn, Dokyoon Kim
Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI)...
February 13, 2019: Scientific Reports
S Andrea Wijtenburg, Dimitrios Kapogiannis, Stephanie A Korenic, Roger J Mullins, Joyce Tran, Frank E Gaston, Shuo Chen, Maja Mustapic, L Elliot Hong, Laura M Rowland
Memory is robustly impaired in schizophrenia (SZ) and related to functional outcome. Memory dysfunction has been shown to be related to altered brain glucose metabolism and brain insulin resistance in animal models and human studies of Alzheimer's disease. In this study, differences in brain glucose using magnetic resonance spectroscopy (MRS) and blood Extracellular Vesicle (EV) biomarkers of neuronal insulin resistance (i.e. Akt and signaling effectors) between SZ and controls were investigated, as well as whether these measures were related to memory impairments...
February 11, 2019: Schizophrenia Research
Xiaoya Liu, Shuang Liu, Dongyue Guo, Yue Sheng, Yufeng Ke, Xingwei An, Feng He, Dong Ming
Objectives : It has been reported recently that gamma measures of the electroencephalogram (EEG) might provide information about the candidate biomarker of mental diseases like schizophrenia, Alzheimer's disease, affective disorder and so on, but as we know it is a difficult issue to induce visual and tactile evoked responses at high frequencies. Although a high-frequency response evoked by auditory senses is achievable, the quality of the recording response is not ideal, such as relatively low signal-to-noise ratio (SNR)...
February 12, 2019: Sensors
David S Knopman, Emily S Lundt, Terry M Therneau, Prashanthi Vemuri, Val J Lowe, Kejal Kantarci, Jeffrey L Gunter, Matthew L Senjem, Michelle M Mielke, Mary M Machulda, Bradley F Boeve, David T Jones, Jon Graff-Radford, Sabrina M Albertson, Christopher G Schwarz, Ronald C Petersen, Clifford R Jack
As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI...
February 12, 2019: Brain: a Journal of Neurology
Brian A Gordon, Tyler M Blazey, Jon Christensen, Aylin Dincer, Shaney Flores, Sarah Keefe, Charles Chen, Yi Su, Eric M McDade, Guoqiao Wang, Yan Li, Jason Hassenstab, Andrew Aschenbrenner, Russ Hornbeck, Clifford R Jack, Beau M Ances, Sarah B Berman, Jared R Brosch, Douglas Galasko, Serge Gauthier, James J Lah, Mario Masellis, Christopher H van Dyck, Mark A Mintun, Gregory Klein, Smiljana Ristic, Nigel J Cairns, Daniel S Marcus, Chengjie Xiong, David M Holtzman, Marcus E Raichle, John C Morris, Randall J Bateman, Tammie L S Benzinger
Tauopathy is a hallmark pathology of Alzheimer's disease with a strong relationship with cognitive impairment. As such, understanding tau may be a key to clinical interventions. In vivo tauopathy has been measured using cerebrospinal fluid assays, but these do not provide information about where pathology is in the brain. The introduction of PET ligands that bind to paired helical filaments provides the ability to measure the amount and distribution of tau pathology. The heritability of the age of dementia onset tied to the specific mutations found in autosomal dominant Alzheimer's disease families provides an elegant model to study the spread of tau across the course of the disease as well as the cross-modal relationship between tau and other biomarkers...
February 11, 2019: Brain: a Journal of Neurology
Hanbi Kim, Jong Uk Lee, Soohyun Kim, Sojin Song, Sang Jun Sim
Blood-based diagnosis (Hemodiagnosis) of Alzheimer's disease (AD) is emerging as a promising alternative of cerebrospinal fluid-based methods because blood contains various kinds of AD biomarkers, including amyloid beta 1-40, 1-42, and τ (tau) protein. However, with current technology, the accuracy of the blood plasma-based methods is relatively low compared to the traditional methods because the concentration of AD biomarkers in blood plasma is incredibly low and diverse interfer-ence is present in blood plasma, which hinders precise detection...
February 12, 2019: ACS Sensors
Ryszard Pluta, Marzena Ułamek-Kozioł
In the aging world population, Alzheimer's disease accounts for more than 70% of all cases of dementia and is the sixth leading cause of death. The neurodegenerative processes of this disorder can begin 10-20 years before the clinical symptoms develop. Postmortem brain autopsy of Alzheimer's disease cases reveals characteristic hallmarks like extracellular amyloid plaques and intraneuronal neurofibrillary tangles and synaptic and neuronal disintegration with severe brain atrophy. Some studies have reported that platelets contain the amyloid protein precursor and the secretase enzymes required for the amyloidogenic processing of this protein...
2019: Advances in Experimental Medicine and Biology
Jeffrey Cummings
Biomarkers have a key role in Alzheimer's disease (AD) drug development. Biomarkers can assist in diagnosis, demonstrate target engagement, support disease modification, and monitor for safety. The amyloid (A), tau (T), neurodegeneration (N) Research Framework emphasizes brain imaging and CSF measures relevant to disease diagnosis and staging and can be applied to drug development and clinical trials. Demonstration of target engagement in Phase 2 is critical before advancing a treatment candidate to Phase 3...
2019: Advances in Experimental Medicine and Biology
Alberto J Espay, Joaquin A Vizcarra, Luca Marsili, Anthony E Lang, David K Simon, Aristide Merola, Keith A Josephs, Alfonso Fasano, Francesca Morgante, Rodolfo Savica, J Timothy Greenamyre, Franca Cambi, Tritia R Yamasaki, Caroline M Tanner, Ziv Gan-Or, Irene Litvan, Ignacio F Mata, Cyrus P Zabetian, Patrik Brundin, Hubert H Fernandez, David G Standaert, Marcelo A Kauffman, Michael A Schwarzschild, S Pablo Sardi, Todd Sherer, George Perry, James B Leverenz
The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death...
February 12, 2019: Neurology
Anna Pedrinolla, Massimo Venturelli, Stefano Tamburin, Cristina Fonte, Anna Maria Stabile, Ilaria Boscolo Galazzo, Barbara Ghinassi, Mary Anna Venneri, Francesca Benedetta Pizzini, Ettore Muti, Nicola Smania, Angela Di Baldassarre, Fabio Naro, Mario Rende, Federico Schena
Recent literature highlights the importance of identifying factors associated with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Actual validated biomarkers include neuroimaging and cerebrospinal fluid assessments; however, we investigated non-Aβ-dependent factors associated with dementia in 12 MCI and 30 AD patients. Patients were assessed for global cognitive function (Mini-Mental state examination-MMSE), physical function (Physical Performance Test-PPT), exercise capacity (6-min walking test-6MWT), maximal oxygen uptake (VO₂max), brain volume, vascular function (flow-mediated dilation-FMD), inflammatory status (tumor necrosis factor-α ,TNF- α, interleukin-6, -10 and -15) and neurotrophin receptors (p75NTR and Tropomyosin receptor kinase A -TrkA)...
February 9, 2019: Journal of Clinical Medicine
Marie Bruun, Juha Koikkalainen, Hanneke F M Rhodius-Meester, Marta Baroni, Le Gjerum, Mark van Gils, Hilkka Soininen, Anne M Remes, Päivi Hartikainen, Gunhild Waldemar, Patrizia Mecocci, Frederik Barkhof, Yolande Pijnenburg, Wiesje M van der Flier, Steen G Hasselbalch, Jyrki Lötjönen, Kristian S Frederiksen
BACKGROUND: Diagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another. METHODS: In this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline...
February 4, 2019: NeuroImage: Clinical
Christina Strand-Holm Manniche, Anne-Mette Hejl, Steen Gregers Hasselbalch, Anja H Simonsen
BACKGROUND: The diagnostic workup of idiopathic normal pressure hydrocephalus (iNPH) can be challenging due to an overlap in symptoms and neuroimaging features with other disorders. Despite a growing interest, a cerebrospinal fluid (CSF) biomarker profile in iNPH has not yet been identified. OBJECTIVE: To determine the CSF biomarkers with the greatest evidence for differentiating iNPH from the most common differential diagnoses, Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD)...
February 7, 2019: Journal of Alzheimer's Disease: JAD
Hong Li, Sue Leurgans, Jordan Elm, Mulugeta Gebregziabher
Alzheimer's disease (AD) is a common, devastating disease which carries a heavy economic burden. Accelerated efforts to identify presymptomatic stages of AD and biomarkers to classify the disease are urgent needs. Currently no biomarkers can perfectly discriminate individuals into multiple disease categories of AD (no cognitive impairment, mild cognitive impairment, and dementia). Although many biomarkers for diagnosis and their various features are being studied, we lack advanced statistical methods which can fully utilize biomarkers to classify AD accurately, thereby facilitating evaluation of putative markers both alone and in combination...
February 7, 2019: Journal of Alzheimer's Disease: JAD
Yusra Mansour, Kaitlyn Blackburn, Luis Oscar González-González, Lilian Calderón-Garcidueñas, Randy J Kulesza
Alzheimer's disease (AD) is a biological construct defined by abnormal deposits of hyperphosphorylated tau and amyloid-β. The 2050 projection for AD in the USA is 14 million. There is a strong association between AD, air pollution, and traffic. Early diagnosis is imperative for intervention in the initial disease stages. Hearing and, specifically, the ability to encode complex sounds are impaired in AD. Nuclei in the auditory brainstem appear to be sensitive to neurodevelopmental and neurodegenerative disorders...
February 2, 2019: Journal of Alzheimer's Disease: JAD
Han Zhang, Panteleimon Giannakopoulos, Sven Haller, Dinggang Shen, Seong-Whan Lee, Shijun Qiu
Little is known about the high-order interactions among brain regions measured by the similarity of higher-order features (other than the raw blood-oxygen-level-dependent signals) which can characterize higher-level brain functional connectivity (FC). Previously, we proposed FC topographical profile-based high-order FC (HOFC) and found that this metric could provide supplementary information to traditional FC for early Alzheimer's disease (AD) detection. However, whether such findings apply to network-level brain functional integration is unknown...
February 9, 2019: Neuroinformatics
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