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https://www.readbyqxmd.com/read/28738127/early-onset-alzheimer-disease-and-candidate-risk-genes-involved-in-endolysosomal-transport
#1
Brian W Kunkle, Badri N Vardarajan, Adam C Naj, Patrice L Whitehead, Sophie Rolati, Susan Slifer, Regina M Carney, Michael L Cuccaro, Jeffery M Vance, John R Gilbert, Li-San Wang, Lindsay A Farrer, Christiane Reitz, Jonathan L Haines, Gary W Beecham, Eden R Martin, Gerard D Schellenberg, Richard P Mayeux, Margaret A Pericak-Vance
Importance: Mutations in APP, PSEN1, and PSEN2 lead to early-onset Alzheimer disease (EOAD) but account for only approximately 11% of EOAD overall, leaving most of the genetic risk for the most severe form of Alzheimer disease unexplained. This extreme phenotype likely harbors highly penetrant risk variants, making it primed for discovery of novel risk genes and pathways for AD. Objective: To search for rare variants contributing to the risk for EOAD. Design, Setting, and Participants: In this case-control study, whole-exome sequencing (WES) was performed in 51 non-Hispanic white (NHW) patients with EOAD (age at onset <65 years) and 19 Caribbean Hispanic families previously screened as negative for established APP, PSEN1, and PSEN2 causal variants...
July 24, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28736521/group-level-progressive-alterations-in-brain-connectivity-patterns-revealed-by-diffusion-tensor-brain-networks-across-severity-stages-in-alzheimer-s-disease
#2
Javier Rasero, Carmen Alonso-Montes, Ibai Diez, Laiene Olabarrieta-Landa, Lakhdar Remaki, Iñaki Escudero, Beatriz Mateos, Paolo Bonifazi, Manuel Fernandez, Juan Carlos Arango-Lasprilla, Sebastiano Stramaglia, Jesus M Cortes
Alzheimer's disease (AD) is a chronically progressive neurodegenerative disease highly correlated to aging. Whether AD originates by targeting a localized brain area and propagates to the rest of the brain across disease-severity progression is a question with an unknown answer. Here, we aim to provide an answer to this question at the group-level by looking at differences in diffusion-tensor brain networks. In particular, making use of data from Alzheimer's Disease Neuroimaging Initiative (ADNI), four different groups were defined (all of them matched by age, sex and education level): G1 (N1 = 36, healthy control subjects, Control), G2 (N2 = 36, early mild cognitive impairment, EMCI), G3 (N3 = 36, late mild cognitive impairment, LMCI) and G4 (N4 = 36, AD)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28733957/a-review-of-biomarkers-for-alzheimer-s-disease-in-down-syndrome
#3
REVIEW
Ni-Chung Lee, Yin-Hsiu Chien, Wuh-Liang Hwu
Down syndrome (Trisomy 21; DS) is a unique disease known to be associated with early-onset Alzheimer's disease (AD). The initial presentation of AD in DS is usually difficult to recognize, owing to the underlying intellectual disabilities. Using biomarkers as a prediction tool for detecting AD in at-risk people with DS may benefit patient care. The objective of this review is to discuss the utility of biomarkers in DS on the basis of the pathophysiology of the disease and to provide an update on recent studies in this field...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733955/detection-of-plasma-biomarkers-using-immunomagnetic-reduction-a-promising-method-for-the-early-diagnosis-of-alzheimer-s-disease
#4
REVIEW
Shieh-Yueh Yang, Ming-Jang Chiu, Ta-Fu Chen, Herng-Er Horng
Alzheimer's disease (AD) is the most common form of dementia. The development of assay technologies able to diagnose early-stage AD is important. Blood tests to detect biomarkers, such as amyloid and total Tau protein, are among the most promising diagnostic methods due to their low cost, low risk, and ease of operation. However, such biomarkers in blood occur at extremely low levels and are difficult to detect precisely. In the early 2000s, a highly sensitive assay technology, immunomagnetic reduction (IMR), was developed...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733268/carriers-of-an-apolipoprotein-e-epsilon-4-allele-are-more-vulnerable-to-a-dietary-deficiency-in-omega-3-fatty-acids-and-cognitive-decline
#5
REVIEW
Tanya Gwendolyn Nock, Raphaël Chouinard-Watkins, Mélanie Plourde
Carriers of an epsilon 4 allele (E4) of apolipoprotein E (APOE) develop Alzheimer's disease (AD) earlier than carriers of other APOE alleles. The metabolism of plasma docosahexaenoic acid (DHA, 22:6n-3), an omega-3 fatty acid (n-3 FA), taken up by the brain and concentrated in neurons, is disrupted in E4 carriers, resulting in lower levels of brain DHA. Behavioural and cognitive impairments have been observed in animals with lower brain DHA levels, with emphasis on loss of spatial memory and increased anxiety...
July 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28731444/the-relationship-of-brain-amyloid-load-and-apoe-status-to-regional-cortical-thinning-and-cognition-in-the-adni-cohort
#6
Chunfei Li, David A Loewenstein, Ranjan Duara, Mercedes Cabrerizo, Warren Barker, Malek Adjouadi
BACKGROUND: Both amyloid (Aβ) load and APOE4 allele are associated with neurodegenerative changes in Alzheimer's disease (AD) prone regions and with risk for cognitive impairment. OBJECTIVE: To evaluate the unique and independent contribution of APOE4 allele status (E4+∖E4-), Aβ status (Amy+∖Amy-), and combined APOE4 and Aβ status on regional cortical thickness (CoTh) and cognition among participants diagnosed as cognitively normal (CN, n = 251), early mild cognitive impairment (EMCI, n = 207), late mild cognitive impairment (LMCI, n = 196), and mild AD (n = 162) from the ADNI...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731435/identification-of-circulating-mir-125b-as-a-potential-biomarker-of-alzheimer-s-disease-in-app-ps1-transgenic-mouse
#7
Honghai Hong, Yang Li, Baochang Su
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive decline in cognitive abilities of the affected individuals. Biological markers are essential to identify individuals at early stages of the disease for timely therapeutic intervention. Currently, pathological biomarkers are detected either through cerebrospinal fluid analysis or brain imaging, or postmortem, all of which are expensive, invasive, or time consuming. Recently, some studies have shown that circulating miR-125b, miR-181c, miR-9, miR-191-5p, miR-26b-3p, and miR-28-3p may be biomarkers of AD...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731433/the-effects-of-cardiotrophin-1-on-early-synaptic-mitochondrial-dysfunction-and-synaptic-pathology-in-appswe-ps1de9-mice
#8
Dongmei Wang, Xiaozhuan Liu, Yumei Liu, Sanqiang Li, Chenying Wang
The coexistence of neuronal mitochondrial pathology and synaptic dysfunction is an early pathological feature of Alzheimer's disease (AD). Cardiotrophin-1 (CT-1) has been shown to exhibit impressive neuroprotective effects. Previous studies have shown positive effects of CT-1 on brain glucose metabolism and cognition in APPswe/PS1dE9 transgenic mice; however, little is known about the effects of CT-1 on early synaptic mitochondrial dysfunction and resultant synaptic pathology in the brain. In this study, 4-month-old transgenic mice with brain tissue-specific CT-1 expression were used alone or in combination with APPswe/PS1dE9 transgenic mice to evaluate the effect of CT-1 on synaptic mitochondrial dysfunction and resultant synaptic pathology, and cryptic memory deficits in the APPswe/PS1dE9 transgenic mice...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731429/severity-of-depression-impacts-imminent-conversion-from-mild-cognitive-impairment-to-alzheimer-s-disease
#9
Michaela Defrancesco, Josef Marksteiner, Georg Kemmler, Walter Wolfgang Fleischhacker, Imrich Blasko, Eberhard A Deisenhammer
BACKGROUND: Mild cognitive impairment (MCI) has been suggested to represent a prodromal stage of dementia and to confer a high risk for conversion to dementia Alzheimer's type (DAT). OBJECTIVES: In this study, we examined the predictive value of depressive symptoms and neuropsychological variables on conversion of MCI to DAT. METHODS: Neuropsychological and clinical follow-up data of 260 MCI patients seen at the Psychiatric Memory Clinic of the Medical University of Innsbruck between 2005 and 2015 were analyzed retrospectively...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28730955/itraq-based-proteomic-analysis-of-appsw-ind-mice-provides-insights-into-the-early-changes-in-alzheimer-s-disease
#10
Nan Li, Pinghong Hu, Tiantian Xu, Huan Chen, Xiaoying Chen, Jianwen Hu, Xifei Yang, Lei Shi, Jian-Hong Luo, Junyu Xu
BACKGROUND: Several proteins have been identified as potential diagnostic biomarkers in imaging, genetic, or proteomic studies in Alzheimer disease (AD) patients and mouse models. However, biomarkers for presymptom diagnosis of AD are still under investigation, as are the presymptom molecular changes in AD pathogenesis. OBJECTIVE: In this study, we aim to analyzed the early proteomic changes in APPSw,Ind mice and to conduct further functional studies on interesting proteins...
July 19, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28725932/dna-methylation-in-elovl2-and-c1orf132-correctly-predicted-chronological-age-of-individuals-from-three-disease-groups
#11
M Spólnicka, E Pośpiech, B Pepłońska, R Zbieć-Piekarska, Ż Makowska, A Pięta, J Karłowska-Pik, B Ziemkiewicz, M Wężyk, P Gasperowicz, T Bednarczuk, M Barcikowska, C Żekanowski, R Płoski, Wojciech Branicki
Improving accuracy of the available predictive DNA methods is important for their wider use in routine forensic work. Information on age in the process of identification of an unknown individual may provide important hints that can speed up the process of investigation. DNA methylation markers have been demonstrated to provide accurate age estimation in forensics, but there is growing evidence that DNA methylation can be modified by various factors including diseases. We analyzed DNA methylation profile in five markers from five different genes (ELOVL2, C1orf132, KLF14, FHL2, and TRIM59) used for forensic age prediction in three groups of individuals with diagnosed medical conditions...
July 19, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28722438/graphene-oxide-upconversion-nanoparticle-based-optical-sensors-for-targeted-detection-of-mrna-biomarkers-present-in-alzheimer-s-disease-and-prostate-cancer
#12
Patrick Vilela, Afaf El-Sagheer, Timothy M Millar, Tom Brown, Otto L Muskens, Antonios G Kanaras
The development of new sensors for the accurate detection of biomarkers in biological fluids is of utmost importance for the early diagnosis of diseases. Next to advanced laboratory techniques, there is a need for relatively simple methods which can significantly broaden the availability of diagnostic capability. Here, we demonstrate the successful application of a sensor platform based on graphene oxide and upconversion nanoparticles (NPs) for the specific detection of mRNA-related oligonucleotide markers in complex biological fluids...
January 27, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722437/surface-plasmon-resonance-clinical-biosensors-for-medical-diagnostics
#13
Jean-Francois Masson
The design and application of sensors for monitoring biomolecules in clinical samples is a common goal of the sensing research community. Surface plasmon resonance (SPR) and other plasmonic techniques such as localized surface plasmon resonance (LSPR) and imaging SPR are reaching a maturity level sufficient for their application in monitoring biomolecules in clinical samples. In recent years, the first examples for monitoring antibodies, proteins, enzymes, drugs, small molecules, peptides, and nucleic acids in biofluids collected from patients afflicted with a series of medical conditions (Alzheimer's, hepatitis, diabetes, leukemia, and cancers such as prostate and breast cancers, among others) demonstrate the progress of SPR sensing in clinical chemistry...
January 27, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28721928/strategic-roadmap-for-an-early-diagnosis-of-alzheimer-s-disease-based-on-biomarkers
#14
REVIEW
Giovanni B Frisoni, Marina Boccardi, Frederik Barkhof, Kaj Blennow, Stefano Cappa, Konstantinos Chiotis, Jean-Francois Démonet, Valentina Garibotto, Panteleimon Giannakopoulos, Anton Gietl, Oskar Hansson, Karl Herholz, Clifford R Jack, Flavio Nobili, Agneta Nordberg, Heather M Snyder, Mara Ten Kate, Andrea Varrone, Emiliano Albanese, Stefanie Becker, Patrick Bossuyt, Maria C Carrillo, Chiara Cerami, Bruno Dubois, Valentina Gallo, Ezio Giacobini, Gabriel Gold, Samia Hurst, Anders Lönneborg, Karl-Olof Lovblad, Niklas Mattsson, José-Luis Molinuevo, Andreas U Monsch, Urs Mosimann, Alessandro Padovani, Agnese Picco, Corinna Porteri, Osman Ratib, Laure Saint-Aubert, Charles Scerri, Philip Scheltens, Jonathan M Schott, Ida Sonni, Stefan Teipel, Paolo Vineis, Pieter Jelle Visser, Yutaka Yasui, Bengt Winblad
The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care...
August 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28721032/-11-c-pib-pet-imaging-reveals-that-amyloid-deposition-in-cases-with-early-onset-alzheimer-s-disease-in-the-absence-of-known-mutations-retains-higher-levels-of-pib-in-the-basal-ganglia
#15
Young Chul Youn, Jae-Won Jang, Su-Hyun Han, HyeRyoun Kim, Ju-Won Seok, Jun Soo Byun, Kwang-Yeol Park, Seong Soo A An, In Kook Chun, SangYun Kim
PURPOSE: Early-onset Alzheimer's disease (EOAD) has a different pathologic burden and clinical features compared with late-onset Alzheimer's disease (LOAD). We examined the effects of age at onset on the burden and distribution of β-amyloid in patients with EOAD, in whom well-characterized mutations associated with Alzheimer's disease were absent. METHODS: We genotyped ApoE, APP, PSEN1 and PSEN2 in the patients with Alzheimer's disease: 9 patients with EOAD (age <65), 11 with LOAD (age >70) and 8 normal controls (NCs), all of whom had undergone (11)C-labeled Pittsburgh compound B-positron emission tomography imaging...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28720893/nanoplasmonic-fiber-tip-probe-detects-significant-reduction-of-intracellular-alzheimer-s-disease-related-oligomers-by-curcumin
#16
Feng Liang, Yu Wan, Diane Schaak, Joseph Ward, Xunuo Shen, Rudolph E Tanzi, Can Zhang, Qimin Quan
Considerable evidence shows critical roles of intracellular pathogenic events of Alzheimer's disease (AD). In particular, intracellular amyloid-β accumulation and oligomerization are early AD pathologic processes, which may lead to changes in inflammatory molecules and other AD-related pathological components. Curcumin and its analogs have been identified as potential drug candidates for AD. However, the effects of curcumin on intracellular AD pathologic processes remain largely unknown. Here we utilized a recently developed nanoplasmonic fiber tip probe (nFTP) technology and investigated whether curcumin leads to intracellular AD pathologic changes...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719622/characterization-of-plasma-metal-profiles-in-alzheimer-s-disease-using-multivariate-statistical-analysis
#17
Chunmei Guan, Rui Dang, Yu Cui, Liyan Liu, Xiaobei Chen, Xiaoyu Wang, Jingli Zhu, Donggang Li, Junwei Li, Decai Wang
The exact cause of Alzheimer's disease (AD) and the role of metals in its etiology remain unclear. We have used an analytical approach, based on inductively coupled plasma mass spectrometry coupled with multivariate statistical analysis, to study the profiles of a wide range of metals in AD patients and healthy controls. AD cannot be cured and the lack of sensitive biomarkers that can be used in the early stages of the disease may contribute to this treatment failure. In the present study, we measured plasma levels of amyloid-β1-42(0...
2017: PloS One
https://www.readbyqxmd.com/read/28717130/polymicrobial-infections-in-brain-tissue-from-alzheimer-s-disease-patients
#18
Diana Pisa, Ruth Alonso, Ana M Fernández-Fernández, Alberto Rábano, Luis Carrasco
Several studies have advanced the idea that the etiology of Alzheimer's disease (AD) could be microbial in origin. In the present study, we tested the possibility that polymicrobial infections exist in tissue from the entorhinal cortex/hippocampus region of patients with AD using immunohistochemistry (confocal laser scanning microscopy) and highly sensitive (nested) PCR. We found no evidence for expression of early (ICP0) or late (ICP5) proteins of herpes simplex virus type 1 (HSV-1) in brain sections. A polyclonal antibody against Borrelia detected structures that appeared not related to spirochetes, but rather to fungi...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716532/multivariate-analyses-of-peripheral-blood-leukocyte-transcripts-distinguish-alzheimer-s-parkinson-s-control-and-those-at-risk-for-developing-alzheimer-s
#19
Elaine Delvaux, Diego Mastroeni, Jennifer Nolz, Nienwen Chow, Marwan Sabbagh, Richard J Caselli, Eric M Reiman, Frederick J Marshall, Paul D Coleman
The need for a reliable, simple, and inexpensive blood test for Alzheimer's disease (AD) suitable for use in a primary care setting is widely recognized. This has led to a large number of publications describing blood tests for AD, which have, for the most part, not been replicable. We have chosen to examine transcripts expressed by the cellular, leukocyte compartment of blood. We have used hypothesis-based cDNA arrays and quantitative PCR to quantify the expression of selected sets of genes followed by multivariate analyses in multiple independent samples...
June 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28715661/cognitive-decline-and-brain-amyloid-%C3%AE-accumulation-across-3-years-in-adults-with-down-syndrome
#20
Sigan L Hartley, Benjamin L Handen, Darlynne Devenny, Iulia Mihaila, Regina Hardison, Patrick J Lao, William E Klunk, Peter Bulova, Sterling C Johnson, Bradley T Christian
Adults with Down syndrome (DS) have a high incidence of Alzheimer's disease (AD), providing a unique opportunity to explore the early, preclinical stages of AD neuropathology. We examined change in brain amyloid-β accumulation via the positron emission tomography tracer [11C] Pittsburgh compound B (PiB) across 2 data collection cycles, spaced 3 years apart, and decline in cognitive functioning in 58 adults with DS without clinical AD. PiB retention increased in the anterior cingulate gyrus, precuneus cortex, parietal cortex, and anterior ventral striatum...
June 2, 2017: Neurobiology of Aging
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