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https://www.readbyqxmd.com/read/28933272/evaluation-of-metabolic-and-synaptic-dysfunction-hypotheses-of-alzheimer-s-disease-ad-a-meta-analysis-of-csf-markers
#1
Roni Manyevitch, Matthew Protas, Sean Scarpiello, Marisa Deliso, Brittany Bass, Anthony Nanajian, Matthew Chang, Stefani M Thompson, Neil Khoury, Rachel Gonnella, Margit Trotz, D Blaine Moore, Emily Harms, George Perry, Lucy Clunes, Angélica Ortiz, Jan O Friedrich, Ian V J Murray
BACKGROUND: Alzheimer's disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focusing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and metabolic dysfunction are increasingly implicated in AD. OBJECTIVE: Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF...
September 21, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28902409/binswanger-s-disease-biomarkers-in-the-inflammatory-form-of-vascular-cognitive-impairment-and-dementia
#2
REVIEW
Gary A Rosenberg
Vascular cognitive impairment and dementia (VCID) is a major public health concern because of the increased incidence of vascular disease in the aging population and the impact of vascular disease on Alzheimer's disease. VCID is a heterogeneous group of diseases for which there are no proven treatments. Biomarkers can be used to select more homogeneous populations. Small vessel disease is the most prevalent form of VCID and is the optimal form for treatment trials because there is a progressive course with characteristic pathological changes...
September 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28900724/hypothalamic-dysfunction-is-related-to-sleep-impairment-and-csf-biomarkers-in-alzheimer-s-disease
#3
Claudio Liguori, Agostino Chiaravalloti, Marzia Nuccetelli, Francesca Izzi, Giuseppe Sancesario, Andrea Cimini, Sergio Bernardini, Orazio Schillaci, Nicola Biagio Mercuri, Placidi Fabio
Hypothalamus is a key brain region regulating several essential homeostatic functions, including the sleep-wake cycle. Alzheimer's disease (AD) pathology affects nuclei controlling sleep-wake rhythm sited in this brain area. Since only post-mortem studies documented the relationship between hypothalamic atrophy and sleep-wake cycle impairment, we investigated in AD patients the possible hypothalamic in vivo alteration using 2-deoxy-2-(18F) fluoro-D-glucose ([18F]FDG) positron emission tomography ([18F]FDG PET), and its correlations with sleep impairment and cerebrospinal-fluid (CSF) AD biomarkers (tau proteins and β-amyloid42)...
September 12, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28900366/tau-protein-as-a-possible-marker-of-cerebrospinal-fluid-leakage-in-cerebrospinal-fluid-rhinorrhoea-a-pilot-study
#4
Jean-Baptiste Oudart, Laure Zucchini, François-Xavier Maquart, Xavier Dubernard, Marc Labrousse, Géraldine Fiabane, Alexandra Quedreux, Fabien Litre, Laurent Ramont
INTRODUCTION: The management of posttraumatic cerebrospinal fluid (CSF) rhinorrhoea remains a clinical challenge. Cerebrospinal fistula is a dural defect responsible for possible CSF leakage into the contiguous air-filled cavities located at the skull base. The risk of central nervous system infection in these conditions is severe and can be life threatening. Consequently, a specific CSF biomarker might be used in case of difficult diagnosis of CSF rhinorrhoea. CSF Tau protein is a neuronal protein, commonly assessed for diagnosis of Alzheimer Disease (AD)...
October 15, 2017: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
https://www.readbyqxmd.com/read/28899429/amyloid-independent-atrophy-patterns-predict-time-to-progression-to-dementia-in-mild-cognitive-impairment
#5
Mara Ten Kate, Frederik Barkhof, Pieter Jelle Visser, Charlotte E Teunissen, Philip Scheltens, Wiesje M van der Flier, Betty M Tijms
BACKGROUND: Amyloid pathology in subjects with mild cognitive impairment (MCI) is an important risk factor for progression to dementia due to Alzheimer's disease. Predicting the onset of dementia is challenging even in the presence of amyloid, as time to progression varies considerably among patients and depends on the onset of neurodegeneration. Survival analysis can account for variability in time to event, but has not often been applied to MRI measurements beyond singular predefined brain regions such as the hippocampus...
September 12, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28893185/factors-that-influence-the-levels-of-cerebrospinal-fluid-biomarkers-in-memory-clinic-patients
#6
Anne-Brita Knapskog, Rannveig Sakshaug Eldholm, Anne Braekhus, Knut Engedal, Ingvild Saltvedt
BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ), phospho tau (P-tau) and total tau (T-tau) are used increasingly to support a clinical diagnosis of Alzheimer's disease. The diagnostic power of these biomarkers has been reported to vary among different studies' results. The results are poorer when heterogeneous groups of patients have been included compared to studies where patients with Alzheimer's dementia (AD) and healthy controls have been studied. The aim of this study was to examine if age, APOE genotype and sex were associated with the levels of CSF biomarkers among patients referred to a memory clinic...
September 11, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28889317/the-predictive-value-of-t-tau-and-ab1-42-levels-in-idiopathic-normal-pressure-hydrocephalus
#7
Claudia L Craven, Irene Baudracco, Henrik Zetterberg, Michael P T Lunn, Miles D Chapman, Neghat Lakdawala, Laurence D Watkins, Ahmed K Toma
BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) has no reliable biomarker to assist in the selection of patients who could benefit from ventriculo-peritoneal (VP) shunt insertion. The neurodegenerative markers T-tau and Aβ1-42 have been found to successfully differentiate between Alzheimer's disease (AD) and INPH and therefore are candidate biomarkers for prognosis and shunt response in INPH. The aim of this study was to test the predictive value of cerebrospinal fluid (CSF) T-tau and Aβ1-42 for shunt responsiveness...
September 9, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28887373/optical-coherence-tomography-identifies-outer-retina-thinning-in-frontotemporal-degeneration
#8
Benjamin J Kim, David J Irwin, Delu Song, Ebenezer Daniel, Jennifer D Leveque, Aaishah R Raquib, Wei Pan, Gui-Shuang Ying, Tomas S Aleman, Joshua L Dunaief, Murray Grossman
OBJECTIVE: Whereas Alzheimer disease (AD) is associated with inner retina thinning visualized by spectral-domain optical coherence tomography (SD-OCT), we sought to determine if the retina has a distinguishing biomarker for frontotemporal degeneration (FTD). METHODS: Using a cross-sectional design, we examined retinal structure in 38 consecutively enrolled patients with FTD and 44 controls using a standard SD-OCT protocol. Retinal layers were segmented with the Iowa Reference Algorithm...
September 8, 2017: Neurology
https://www.readbyqxmd.com/read/28886705/cognitive-function-in-very-old-men-does-not-correlate-to-biomarkers-of-alzheimer-s-disease
#9
V Velickaite, V Giedraitis, K Ström, I Alafuzoff, H Zetterberg, L Lannfelt, L Kilander, E-M Larsson, M Ingelsson
BACKGROUND: The Alzheimer's disease (AD) brain displays atrophy with amyloid-β (Aβ) and tau deposition, whereas decreased Aβ42 and increased tau are measured in cerebrospinal fluid (CSF). The aim of this study was to relate cognitive performance to the degree of brain atrophy, CSF biomarker levels and neuropathology in a cohort of aged men. METHODS: Fifty-eight 86-92-year-old men from the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort underwent cognitive testing, brain computed tomography and lumbar puncture...
September 8, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28879085/progressive-medial-temporal-lobe-atrophy-during-preclinical-alzheimer-s-disease
#10
Corinne Pettigrew, Anja Soldan, Kelly Sloane, Qing Cai, Jiangxia Wang, Mei-Cheng Wang, Abhay Moghekar, Michael I Miller, Marilyn Albert
This study examined whether longitudinal MRI trajectories in medial temporal lobe (MTL) brain regions differed among groups of cognitively normal individuals defined by their cerebrospinal fluid (CSF) levels when they were first enrolled (N = 207; mean clinical follow-up = 13.3 years (max = 20 years), mean MRI follow-up = 2.4 years (max = 8 years)). We first compared atrophy rates among groups defined by CSF amyloid and phosphorylated-tau (p-tau) vs. CSF amyloid and total tau (t-tau). We also examined whether, in the presence of amyloid or tau/p-tau, the atrophy rates differed based on whether the subjects ultimately progressed to a diagnosis of mild cognitive impairment (MCI), as well as whether apolipoprotein ε4 (Apoε4) status had an impact on the longitudinal MRI trajectories...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28869481/alzheimer-s-disease-diagnosis-relies-on-a-twofold-clinical-biological-algorithm-three-memory-clinic-case-reports
#11
Marcel Levy Nogueira, Dalila Samri, Stéphane Epelbaum, Simone Lista, Per Suppa, Lothar Spies, Harald Hampel, Bruno Dubois, Marc Teichmann
The International Working Group recently provided revised criteria of Alzheimer's disease (AD) proposing that the diagnosis of typical amnesic AD should be established by a clinical-biological signature, defined by the phenotype of an "amnesic syndrome of the hippocampal type" (ASHT) combined with positive in vivo evidence of AD pathophysiology in the cerebrospinal fluid (CSF) or on amyloid PET imaging. The application and clinical value of this refined diagnostic algorithm, initially intended for research purposes, is explored in three memory clinic cases presenting with different cognitive profiles including an ASHT, hippocampal atrophy, and CSF AD-biomarker data...
August 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28869470/the-cerebrospinal-fluid-a%C3%AE-1-42-a%C3%AE-1-40-ratio-improves-concordance-with-amyloid-pet-for-diagnosing-alzheimer-s-disease-in-a-clinical-setting
#12
Ellis Niemantsverdriet, Julie Ottoy, Charisse Somers, Ellen De Roeck, Hanne Struyfs, Femke Soetewey, Jeroen Verhaeghe, Tobi Van den Bossche, Sara Van Mossevelde, Johan Goeman, Peter Paul De Deyn, Peter Mariën, Jan Versijpt, Kristel Sleegers, Christine Van Broeckhoven, Leonie Wyffels, Adrien Albert, Sarah Ceyssens, Sigrid Stroobants, Steven Staelens, Maria Bjerke, Sebastiaan Engelborghs
BACKGROUND: Evidence suggests that the concordance between amyloid-PET and cerebrospinal fluid (CSF) amyloid-β (Aβ) increases when the CSF Aβ1-42/Aβ1-40 ratio is used as compared to CSF Aβ1-42 levels alone. OBJECTIVE: In order to test this hypothesis, we set up a prospective longitudinal study comparing the concordance between different amyloid biomarkers for Alzheimer's disease (AD) in a clinical setting. METHODS: Seventy-eight subjects (AD dementia (n = 17), mild cognitive impairment (MCI, n = 48), and cognitively healthy controls (n = 13)) underwent a [18F]Florbetapir ([18F]AV45) PET scan, [18F]FDG PET scan, MRI scan, and an extensive neuropsychological examination...
September 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28869463/risk-factors-neuroanatomical-correlates-and-outcome-of-neuropsychiatric-symptoms-of-alzheimer-s-disease
#13
Stéphane P Poulin, David Bergeron, Bradford C Dickerson
BACKGROUND: An integrative model of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) is lacking. OBJECTIVE: In this study, we aimed to investigate the risk factors, anatomy, biology, and outcomes of NPS in AD. METHODS: 181 subjects were included from the Alzheimer's Disease Neuroimaging Study (ADNI). NPS were assessed with the Neuropsychiatric Inventory Questionnaire at baseline and 6 months. NPI >3 was used as a threshold for NPS positivity...
September 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28868067/cerebrospinal-fluid-apolipoprotein-e-levels-in-delirium
#14
Gideon A Caplan, JIan Tai, Fazrul Mohd Hanizan, Catherine L McVeigh, Mark A Hill, Anne Poljak
BACKGROUND/AIMS: Delirium and the apolipoprotein E ε4 allele are risk factors for late-onset Alzheimer disease (LOAD), but the connection is unclear. We looked for an association. METHODS: Inpatients with delirium (n = 18) were compared with LOAD outpatients (n = 19), assaying blood and cerebrospinal fluid (CSF) using multiplex ELISA. RESULTS: The patients with delirium had a higher Confusion Assessment Method (CAM) score (5.6 ± 1.2 vs. 0...
May 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/28866979/quantification-of-plasma-phosphorylated-tau-to-use-as-a-biomarker-for-brain-alzheimer-pathology-pilot-case-control-studies-including-patients-with-alzheimer-s-disease-and-down-syndrome
#15
Harutsugu Tatebe, Takashi Kasai, Takuma Ohmichi, Yusuke Kishi, Tomoshi Kakeya, Masaaki Waragai, Masaki Kondo, David Allsop, Takahiko Tokuda
BACKGROUND: There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer's disease (AD) pathology. This study is aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181) is informative in the diagnosis of AD. METHODS: We have developed a novel ultrasensitive immunoassay to quantify plasma p-tau181, and measured the levels of plasma p-tau181 in three cohorts. RESULTS: In the first cohort composed of 20 AD patients and 15 age-matched controls, the plasma levels of p-tau181 were significantly higher in the AD patients than those in the controls (0...
September 4, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28866757/levels-of-amyloid-beta-42-and-csf-pressure-are-directly-related-in-patients-with-alzheimer-s-disease
#16
Tommaso Schirinzi, Giulia Di Lazzaro, Giulia Maria Sancesario, Vito Luigi Colona, Eugenia Scaricamazza, Nicola Biagio Mercuri, Alessandro Martorana, Giuseppe Sancesario
Experimental data suggest that the cerebrospinal fluid (CSF) dynamic is involved in the clearance of beta-amyloid, a key event in the pathogenesis of Alzheimer's disease (AD). At this regard no evidence still exists in vivo. In this study we explored the relationships between CSF pressure and AD pathology, as measured with CSF core biomarkers. We enrolled 16 patients with probable AD and 21 controls, collecting demographics, clinical data, CSF opening pressure and CSF levels of beta-amyloid-42 fragment (Aβ42), total-tau (t-tau), phosphorylated-tau-181 (p-tau), albumin and albumin ratio...
September 2, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28861336/a-whole-brain-computational-modeling-approach-to-explain-the-alterations-in-resting-state-functional-connectivity-during-progression-of-alzheimer-s-disease
#17
Murat Demirtaş, Carles Falcon, Alan Tucholka, Juan Domingo Gispert, José Luis Molinuevo, Gustavo Deco
Alzheimer's disease (AD) is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC) of the subjects with preclinical Alzheimer's disease (PAD), mild cognitive impairment due to AD (MCI) and mild dementia due to Alzheimer's disease (AD), the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28860054/detection-of-contactin-2-in-cerebrospinal-fluid-csf-of-patients-with-alzheimer-s-disease-using-fluorescence-correlation-spectroscopy-fcs
#18
Madhurima Chatterjee, Bernd Nöding, Eline A J Willemse, Marleen J A Koel-Simmelink, Wiesje M van der Flier, Detlev Schild, Charlotte E Teunissen
OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia in the world. As many AD biomarkers occur at rather low abundances in CSF or blood, techniques of very high sensitivity and accuracy are important as diagnostic tools in the clinic. Here, we aimed to provide proof of concept of the use of a single molecule detection technique, Fluorescence Correlation Spectroscopy (FCS) for detection of novel candidate biomarkers for AD. DESIGN AND METHODS: FCS detects the diffusion times of the antigen-antibody complexes in highly diluted sample solutions, thus eliminating the need of large sample volumes and allows estimating the concentration of the target antigen...
August 28, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28856569/pharmacokinetics-of-cromolyn-and-ibuprofen-in-healthy-elderly-volunteers
#19
David Brazier, Robert Perry, Jim Keane, Katie Barrett, David R Elmaleh
BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being investigated as a treatment for early Alzheimer's disease (AD). This study investigated the pharmacokinetics, safety, and tolerability of cromolyn and ibuprofen co-administration in healthy elderly adult volunteers. METHODS: In this open-labeled study, 26 subjects, aged 55-75 years, received co-administration of inhaled cromolyn (single dose 17.1 mg; double dose 34.2 mg total) and oral ibuprofen (single dose 10 mg; double dose 20 mg total)...
August 30, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28854881/neurogranin-and-tau-in-cerebrospinal-fluid-and-plasma-of-patients-with-acute-ischemic-stroke
#20
Ann De Vos, Maria Bjerke, Raf Brouns, Naomi De Roeck, Dirk Jacobs, Lien Van den Abbeele, Kaat Guldolf, Henrik Zetterberg, Kaj Blennow, Sebastiaan Engelborghs, Eugeen Vanmechelen
BACKGROUND: While neurogranin has no value as plasma biomarker for Alzheimer's disease, it may be a potential blood biomarker for traumatic brain injury. This evokes the question whether there are changes in neurogranin levels in blood in other conditions of brain injury, such as acute ischemic stroke (AIS). METHODS: We therefore explored neurogranin in paired cerebrospinal fluid (CSF)/plasma samples of AIS patients (n = 50) from a well-described prospective study...
August 30, 2017: BMC Neurology
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