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Article ; Online: Biomarkers of Alzheimer's disease and neurodegeneration in dried blood spots-A new collection method for remote settings.

Huber, Hanna / Blennow, Kaj / Zetterberg, Henrik / Boada, Mercé / Jeromin, Andreas / Weninger, Haley / Nuñez-Llaves, Raul / Aguilera, Núria / Ramis, Maribel / Simrén, Joel / Nilsson, Johanna / Lantero-Rodriguez, Juan / Orellana, Adelina / García-Gutiérrez, Fernando / Morató, Xavier / Ashton, Nicholas J / Montoliu-Gaya, Laia

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024 Volume 20, Issue 4, Page(s) 2340–2352

Abstract: Background: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPS: Methods: In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic ... ...

Abstract	Background: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPS Methods: In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic protein (GFAP); neurofilament light (NfL); amyloid beta (Aβ) 40, Aβ42; and phosphorylated tau (p-tau181 and p-tau217) were measured in paired DPS Results: All DPS Discussion: Our data suggest that measuring blood biomarkers related to AD pathology and neurodegeneration from DPS Highlights: A wide array of biomarkers related to Alzheimer's disease (AD) and neurodegeneration were detectable in dried plasma spots (DPS
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides ; Plasma ; Amyloidogenic Proteins ; Biomarkers ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; Amyloidogenic Proteins ; Biomarkers ; tau Proteins
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13697
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Article ; Online: Correlations between the NMR Lipoprotein Profile,

de Rojas, Itziar / Del Barrio, Laura / Hernández, Isabel / Montrreal, Laura / García-González, Pablo / Marquié, Marta / Valero, Sergi / Cano, Amanda / Orellana, Adelina / Boada, Mercè / Mañes, Santos / Ruiz, Agustín

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer's disease. The inactivation of ... ...

Abstract	Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer's disease. The inactivation of the
MeSH term(s)	Animals ; Mice ; Humans ; Male ; Adult ; Aged ; Cholesterol ; Magnetic Resonance Spectroscopy ; Fasting ; Genotype ; Apolipoproteins E/genetics ; Cholesterol, HDL
Chemical Substances	Cholesterol (97C5T2UQ7J) ; Apolipoproteins E ; Cholesterol, HDL
Language	English
Publishing date	2023-01-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032186
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Article ; Online: Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer's disease.

Wang, Lihua / Nykänen, Niko-Petteri / Western, Daniel / Gorijala, Priyanka / Timsina, Jigyasha / Li, Fuhai / Wang, Zhaohua / Ali, Muhammad / Yang, Chengran / Liu, Menghan / Brock, William / Marquié, Marta / Boada, Mercè / Alvarez, Ignacio / Aguilar, Miquel / Pastor, Pau / Ruiz, Agustín / Puerta, Raquel / Orellana, Adelina /

Rutledge, Jarod / Oh, Hamilton / Greicius, Michael D / Le Guen, Yann / Perrin, Richard J / Wyss-Coray, Tony / Jefferson, Angela / Hohman, Timothy J / Graff-Radford, Neill / Mori, Hiroshi / Goate, Alison / Levin, Johannes / Sung, Yun Ju / Cruchaga, Carlos

Molecular neurodegeneration

2024 Volume 19, Issue 1, Page(s) 1

Abstract: Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer's disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble ... ...

Abstract	Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer's disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed the largest genome-wide association study (GWAS) and identified four loci for CSF sTREM2 in 3,350 individuals of European ancestry. Through multi-ethnic fine mapping, we identified two independent missense variants (p.M178V in MS4A4A and p.A112T in MS4A6A) that drive the association in MS4A locus and showed an epistatic effect for sTREM2 levels and AD risk. The novel TREM2 locus on chr 6 contains two rare missense variants (rs75932628 p.R47H, P=7.16×10
MeSH term(s)	Humans ; Alzheimer Disease/pathology ; Receptor, Transforming Growth Factor-beta Type II/genetics ; Genome-Wide Association Study ; Microglia/pathology ; Apolipoproteins E/genetics ; Biomarkers/cerebrospinal fluid ; Membrane Glycoproteins/genetics ; Receptors, Immunologic/genetics
Chemical Substances	Receptor, Transforming Growth Factor-beta Type II (EC 2.7.11.30) ; Apolipoproteins E ; Biomarkers ; TREM2 protein, human ; Membrane Glycoproteins ; Receptors, Immunologic
Language	English
Publishing date	2024-01-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2244557-2
ISSN	1750-1326 ; 1750-1326
ISSN (online)	1750-1326
ISSN	1750-1326
DOI	10.1186/s13024-023-00687-4
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Article: Harnessing acoustic speech parameters to decipher amyloid status in individuals with mild cognitive impairment.

Frontiers in neuroscience

2023 Volume 17, Page(s) 1221401

Abstract: Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive functions. Currently, there are no effective treatments for AD, underscoring the importance of identifying individuals in the preclinical stages of ... ...

Abstract	Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive functions. Currently, there are no effective treatments for AD, underscoring the importance of identifying individuals in the preclinical stages of mild cognitive impairment (MCI) to enable early interventions. Among the neuropathological events associated with the onset of the disease is the accumulation of amyloid protein in the brain, which correlates with decreased levels of A
Language	English
Publishing date	2023-09-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2023.1221401
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Article ; Online: Establishing In-House Cutoffs of CSF Alzheimer's Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort.

International journal of molecular sciences

2022 Volume 23, Issue 13

Abstract: Background: Clinical diagnosis of Alzheimer's disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the ...

Abstract	Background: Clinical diagnosis of Alzheimer's disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing-Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland-Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan-Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates ( Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/psychology ; Amyloid beta-Peptides ; Biomarkers ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/psychology ; Cross-Sectional Studies ; Disease Progression ; Humans ; Peptide Fragments ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments ; tau Proteins
Language	English
Publishing date	2022-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23136891
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Article ; Online: A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging.

Dumurgier, Julien / Sabia, Séverine / Zetterberg, Henrik / Teunissen, Charlotte E / Hanseeuw, Bernard / Orellana, Adelina / Schraen, Susanna / Gabelle, Audrey / Boada, Mercè / Lebouvier, Thibaud / Willemse, Eline A J / Cognat, Emmanuel / Ruiz, Agustin / Hourregue, Claire / Lilamand, Matthieu / Bouaziz-Amar, Elodie / Laplanche, Jean-Louis / Lehmann, Sylvain / Pasquier, Florence /

Scheltens, Philip / Blennow, Kaj / Singh-Manoux, Archana / Paquet, Claire

Neurology

2022 Volume 99, Issue 7, Page(s) e669–e678

Abstract: Background and objectives: To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging.: Methods: Low ... ...

Abstract	Background and objectives: To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging. Methods: Low and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF β-amyloid (Aβ) peptide biomarkers. These Aβ cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients. Results: A total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women). In the ADNI study population (n = 497), the agreement between classification based on our algorithm and the one based on amyloid/tau PET imaging was high, with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n = 6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. Discussion: The proposed novel, pragmatic method to determine CSF biomarker cutoffs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.
MeSH term(s)	Aged ; Alzheimer Disease/diagnostic imaging ; Amyloid beta-Peptides ; Biomarkers/cerebrospinal fluid ; Female ; Humans ; Male ; Peptide Fragments ; Positron-Emission Tomography ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments ; tau Proteins
Language	English
Publishing date	2022-05-26
Publishing country	United States
Document type	Journal Article ; Validation Study ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000200735
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Article ; Online: Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment.

Cano, Amanda / Esteban-de-Antonio, Ester / Bernuz, Mireia / Puerta, Raquel / García-González, Pablo / de Rojas, Itziar / Olivé, Claudia / Pérez-Cordón, Alba / Montrreal, Laura / Núñez-Llaves, Raúl / Sotolongo-Grau, Óscar / Alarcón-Martín, Emilio / Valero, Sergi / Alegret, Montserrat / Martín, Elvira / Martino-Adami, Pamela V / Ettcheto, Miren / Camins, Antonio / Vivas, Assumpta /

Gomez-Chiari, Marta / Tejero, Miguel Ángel / Orellana, Adelina / Tárraga, Lluís / Marquié, Marta / Ramírez, Alfredo / Martí, Mercè / Pividori, María Isabel / Boada, Mercè / Ruíz, Agustín

Journal of nanobiotechnology

2023 Volume 21, Issue 1, Page(s) 54

Abstract: In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p-tau-mediated neuronal injury and a mild cognitive ... ...

Abstract	In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p-tau-mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre-screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma extracellular vesicles (pEVs) are gaining popularity as a new source of biomarkers for the early stages of AD development. To identify an exosome proteomics signature linked to prodromal AD, we performed a cross-sectional study in a cohort of early-onset MCI (EOMCI) patients in which 184 biomarkers were measured in pEVs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink
MeSH term(s)	Humans ; Amyloid beta-Peptides ; Cross-Sectional Studies ; Alzheimer Disease/metabolism ; Cognitive Dysfunction/diagnosis ; tau Proteins/cerebrospinal fluid ; Extracellular Vesicles/metabolism ; Biomarkers ; Peptide Fragments
Chemical Substances	Amyloid beta-Peptides ; tau Proteins ; Biomarkers ; Peptide Fragments
Language	English
Publishing date	2023-02-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2100022-0
ISSN	1477-3155 ; 1477-3155
ISSN (online)	1477-3155
ISSN	1477-3155
DOI	10.1186/s12951-023-01793-7
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Article: Macular vessel density in the superficial plexus is not associated to cerebrospinal fluid core biomarkers for Alzheimer's disease in individuals with mild cognitive impairment: The NORFACE cohort.

Marquié, Marta / García-Sánchez, Ainhoa / Alarcón-Martín, Emilio / Martínez, Joan / Castilla-Martí, Miguel / Castilla-Martí, Luis / Orellana, Adelina / Montrreal, Laura / de Rojas, Itziar / García-González, Pablo / Puerta, Raquel / Olivé, Clàudia / Cano, Amanda / Hernández, Isabel / Rosende-Roca, Maitée / Vargas, Liliana / Tartari, Juan Pablo / Esteban-De Antonio, Ester / Bojaryn, Urszula /

Ricciardi, Mario / Ariton, Diana M / Pytel, Vanesa / Alegret, Montserrat / Ortega, Gemma / Espinosa, Ana / Pérez-Cordón, Alba / Sanabria, Ángela / Muñoz, Nathalia / Lleonart, Núria / Aguilera, Núria / Tárraga, Lluís / Valero, Sergi / Ruiz, Agustín / Boada, Mercè

Frontiers in neuroscience

2023 Volume 17, Page(s) 1076177

Abstract: Background: Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is ... ...

Abstract	Background: Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is essential to validate the former as a marker of cerebrovascular impairment in the AD continuum. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus quantified by OCT-A with the AT(N) classification based on cerebrospinal fluid (CSF) Aβ1-42, p181-tau and t-tau measurements in individuals with mild cognitive impairment (MCI). Materials and methods: Clinical, demographic, ophthalmological, OCT-A and CSF core biomarkers for AD data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences in macular VD in four quadrants (superior, nasal, inferior, and temporal) among three AT(N) groups [Normal, Alzheimer and Suspected non-Alzheimer pathology (SNAP)] were assessed in a multivariate regression model, adjusted for age, Results: The study cohort comprised 144 MCI participants: 66 Normal AT(N), 45 Alzheimer AT(N) and 33 SNAP AT(N). Regression analysis showed no significant association of the AT(N) groups with any of the regional macular VD measures (all, Discussion: Our study showed that macular VD measures were not associated with the AT(N) classification based on CSF biomarkers in patients with MCI, and did not differ between AD and other underlying causes of cognitive decline in our cohort.
Language	English
Publishing date	2023-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2023.1076177
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Article ; Online: The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment.

Marquié, Marta / García-Gutiérrez, Fernando / Orellana, Adelina / Montrreal, Laura / de Rojas, Itziar / García-González, Pablo / Puerta, Raquel / Olivé, Clàudia / Cano, Amanda / Hernández, Isabel / Rosende-Roca, Maitée / Vargas, Liliana / Tartari, Juan Pablo / Esteban-De Antonio, Ester / Bojaryn, Urszula / Ricciardi, Mario / Ariton, Diana M / Pytel, Vanesa / Alegret, Montserrat /

Ortega, Gemma / Espinosa, Ana / Pérez-Cordón, Alba / Sanabria, Ángela / Muñoz, Nathalia / Lleonart, Núria / Aguilera, Núria / García-Sánchez, Ainhoa / Alarcón-Martín, Emilio / Tárraga, Lluís / Ruiz, Agustín / Boada, Mercè / Valero, Sergi

International journal of molecular sciences

2023 Volume 24, Issue 2

Abstract: Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of ... ...

Abstract	Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients.
MeSH term(s)	Humans ; Follow-Up Studies ; Depression/complications ; Alzheimer Disease/pathology ; Cognitive Dysfunction/pathology ; Amyloidosis/complications ; Biomarkers/cerebrospinal fluid ; Disease Progression ; Neuropsychological Tests ; Amyloid beta-Peptides/cerebrospinal fluid
Chemical Substances	Biomarkers ; Amyloid beta-Peptides
Language	English
Publishing date	2023-01-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24021371
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Article ; Online: Different inflammatory signatures based on CSF biomarkers relate to preserved or diminished brain structure and cognition.

Hayek, Dayana / Ziegler, Gabriel / Kleineidam, Luca / Brosseron, Frederic / Nemali, Aditya / Vockert, Niklas / Ravichandran, Kishore A / Betts, Matthew J / Peters, Oliver / Schneider, Luisa-Sophie / Wang, Xiao / Priller, Josef / Altenstein, Slawek / Schneider, Anja / Fliessbach, Klaus / Wiltfang, Jens / Bartels, Claudia / Rostamzadeh, Ayda / Glanz, Wenzel /

Buerger, Katharina / Janowitz, Daniel / Perneczky, Robert / Rauchmann, Boris-Stephan / Teipel, Stefan / Kilimann, Ingo / Laske, Christoph / Mengel, David / Synofzik, Matthis / Munk, Matthias H / Spottke, Annika / Roy, Nina / Roeske, Sandra / Kuhn, Elizabeth / Ramirez, Alfredo / Dobisch, Laura / Schmid, Matthias / Berger, Moritz / Wolfsgruber, Steffen / Yakupov, Renat / Hetzer, Stefan / Dechent, Peter / Ewers, Michael / Scheffler, Klaus / Schott, Björn H / Schreiber, Stefanie / Orellana, Adelina / de Rojas, Itziar / Marquié, Marta / Boada, Mercè / Sotolongo, Oscar / González, Pablo García / Puerta, Raquel / Düzel, Emrah / Jessen, Frank / Wagner, Michael / Ruiz, Augustín / Heneka, Michael T / Maass, Anne

Molecular psychiatry

2024

Abstract: Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory ... ...

Abstract	Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across the clinical spectrum ranging from normal aging to AD. A panel of 16 inflammatory markers, Aβ42/40 and p-tau181 were measured in CSF at baseline in the DZNE DELCODE cohort (n = 295); a longitudinal observational study focusing on at-risk stages of AD. Volumetric maps of gray and white matter (GM/WM; n = 261) and white matter hyperintensities (WMHs, n = 249) were derived from baseline MRIs. Cognitive decline (n = 204) and the rate of change in GM volume was measured in subjects with at least 3 visits (n = 175). A principal component analysis on the CSF markers revealed four inflammatory components (PCs). Of these, the first component PC1 (highly loading on sTyro3, sAXL, sTREM2, YKL-40, and C1q) was associated with older age and higher p-tau levels, but with less pathological Aβ when controlling for p-tau. PC2 (highly loading on CRP, IL-18, complement factor F/H and C4) was related to male gender, higher body mass index and greater vascular risk. PC1 levels, adjusted for AD markers, were related to higher GM and WM volumes, less WMHs, better baseline memory, and to slower atrophy rates in AD-related areas and less cognitive decline. In contrast, PC2 related to less GM and WM volumes and worse memory at baseline. Similar inflammatory signatures and associations were identified in the independent F.ACE cohort. Our data suggest that there are beneficial and detrimental signatures of inflammatory CSF biomarkers. While higher levels of TAM receptors (sTyro/sAXL) or sTREM2 might reflect a protective glia response to degeneration related to phagocytic clearance, other markers might rather reflect proinflammatory states that have detrimental impact on brain integrity.
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-023-02387-3
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