scholarly journals Amyloid-β peptides in cerebrospinal fluid of patients with dementia with Lewy bodies

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Inger van Steenoven ◽  
Wiesje M. van der Flier ◽  
Philip Scheltens ◽  
Charlotte E. Teunissen ◽  
Afina W. Lemstra
Keyword(s):  
Cerebrospinal Fluid ◽  
Dementia With Lewy Bodies ◽  
Mmse Score ◽  
Apoe Genotype ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Aβ Peptide ◽  
Aβ Peptides ◽  
Cognitively Normal ◽  
Normal Controls

Abstract Background One of the major challenges in diagnosing dementia with Lewy bodies (DLB) is the common co-morbid presence of amyloid pathology. To understand the putative role of altered amyloid-β (Aβ) metabolism in dementia with DLB, we analyzed levels of different cerebrospinal fluid (CSF) Aβ peptides (Aβ38, Aβ40, Aβ42) in DLB, Alzheimer’s disease (AD), and cognitively normal controls. Methods CSF from patients with DLB (n = 72; age 68 ± 6 years; 10%F; Mini-mental State examination (MMSE) 23 ± 4), AD (n = 38; age 68 ± 6 years; 8%F; MMSE 22 ± 5), and cognitively normal controls (n = 38; age 67 ± 7 years; 13%F; MMSE 29 ± 2) was analyzed using the Meso Scale Discovery assay for human Aβ peptides. We performed general linear models to compare CSF Aβ peptide levels between groups. Associations between CSF Aβ peptides and MMSE score at baseline and longitudinal changes over time were assessed with linear mixed models. Results For all three CSF Aβ peptides and compared to controls (Aβ38 2676 ± 703 pg/ml, Aβ40 6243 ± 1500 pg/ml, and Aβ42 692 ± 205 pg/ml), we observed lower levels in DLB (Aβ38 2247 ± 638, Aβ40 5432 ± 1340, and Aβ42 441 ± 185, p < 0.05), whereas AD patients showed only lower Aβ42 levels (304 ± 71, p < 0.001). The observed differences in Aβ38 and Aβ40 were independent of co-morbid AD pathology (CSF tau/Aβ42 > 0.52) and APOE genotype. Finally, lower Aβ peptide levels were associated with lower MMSE score (β = 1.02–1.11, p < 0.05). Conclusion We demonstrated different profiles of CSF Aβ reduction in DLB and AD. In particular, while AD is characterized by an isolated drop in Aβ42, DLB comes with reductions in Aβ38, Aβ40, and Aβ42. This suggests that amyloid metabolism is affected in DLB, even in the absence of co-morbid AD pathology.

scholarly journals Cerebrospinal Fluid Hypocretin and Nightmares in Dementia Syndromes

2021 ◽  
pp. 19-25
Author(s):  
Lynn Marie Trotti ◽  
Donald L. Bliwise ◽  
Glenda L. Keating ◽  
David B. Rye ◽  
William T. Hu
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Cholinesterase Inhibitor ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Cognitively Normal ◽  
Dementia Patients ◽  
Sleep Questionnaires ◽  
Sleep Alterations ◽  
Normal Controls

Background/Aims: Hypocretin promotes wakefulness and modulates REM sleep. Alterations in the hypocretin system are increasingly implicated in dementia. We evaluated relationships among hypocretin, dementia biomarkers, and sleep symptoms in elderly participants, most of whom had dementia. Methods: One-hundred twenty-six adults (mean age 66.2 ± 8.4 years) were recruited from the Emory Cognitive Clinic. Diagnoses were Alzheimer disease (AD; n = 60), frontotemporal dementia (FTD; n = 21), and dementia with Lewy bodies (DLB; n = 20). We also included cognitively normal controls (n = 25). Participants and/or caregivers completed sleep questionnaires and lumbar puncture was performed for cerebrospinal fluid (CSF) assessments. Results: Except for sleepiness (worst in DLB) and nocturia (worse in DLB and FTD) sleep symptoms did not differ by diagnosis. CSF hypocretin concentrations were available for 87 participants and normal in 70, intermediate in 16, and low in 1. Hypocretin levels did not differ by diagnosis. Hypocretin levels correlated with CSF total τ levels only in men (r = 0.34; p = 0.02). Lower hypocretin levels were related to frequency of nightmares (203.9 ± 29.8 pg/mL in those with frequent nightmares vs. 240.4 ± 46.1 pg/mL in those without; p = 0.05) and vivid dreams (209.1 ± 28.3 vs. 239.5 ± 47.8 pg/mL; p = 0.014). Cholinesterase inhibitor use was not associated with nightmares or vivid dreaming. Conclusion: Hypocretin levels did not distinguish between dementia syndromes. Disturbing dreams in dementia patients may be related to lower hypocretin concentrations in CSF.

Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis

2012 ◽  
Vol 19 (5) ◽  
pp. 543-552 ◽  
Author(s):  
Kristin Augutis ◽  
Markus Axelsson ◽  
Erik Portelius ◽  
Gunnar Brinkmalm ◽  
Ulf Andreasson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Inflammatory Diseases ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Aβ Peptide ◽  
Aβ Peptides ◽  
App Metabolism ◽  
Disease Modifying

Background: Amyloid precursor protein (APP) and amyloid β (Aβ) peptides are intensely studied in neuroscience and their cerebrospinal fluid (CSF) measurements may be used to track the metabolic pathways of APP in vivo. Reduced CSF levels of Aβ and soluble APP (sAPP) fragments are reported in inflammatory diseases, including multiple sclerosis (MS); but in MS, the precise pathway of APP metabolism and whether it can be affected by disease-modifying treatments remains unclear. Objective: To characterize the CSF biomarkers of APP degradation in MS, including the effects of disease-modifying therapy. Methods: CSF samples from 87 MS patients (54 relapsing–remitting (RR) MS; 33 secondary progressive (SP) MS and 28 controls were analyzed for sAPP and Aβ peptides by immunoassays, plus a subset of samples was analyzed by immunoprecipitation and mass spectrometry (IP-MS). Patients treated with natalizumab or mitoxantrone were examined at baseline, and after 1–2 years of treatment. Results: CSF sAPP and Aβ peptide levels were reduced in MS patients; but they increased again towards normal, after natalizumab treatment. A multivariate model of IP-MS-measured Aβ species separated the SPMS patients from controls, with RRMS patients having intermediate levels. Conclusions: We confirmed and extended our previous observations of altered CSF sAPP and Aβ peptide levels in MS patients. We found that natalizumab therapy may be able to counteract the altered APP metabolism in MS. The CSF Aβ isoform distribution was found to be distinct in SPMS patients, as compared to the controls.

scholarly journals Low-Abundant Cerebrospinal Fluid Proteome Alterations in Dementia with Lewy Bodies

2013 ◽  
Vol 34 (2) ◽  
pp. 387-397 ◽  
Author(s):  
Jana-Katharina Dieks ◽  
Joanna Gawinecka ◽  
Abdul R. Asif ◽  
Daniela Varges ◽  
Karin Gmitterova ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies

scholarly journals Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Brain ◽  
2016 ◽  
Vol 139 (10) ◽  
pp. 2740-2750 ◽  
Author(s):  
Lidia Sarro ◽  
Matthew L. Senjem ◽  
Emily S. Lundt ◽  
Scott A. Przybelski ◽  
Timothy G. Lesnick ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Grey Matter ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Grey Matter Atrophy

scholarly journals VGF Peptides in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies

2019 ◽  
Vol 20 (19) ◽  
pp. 4674 ◽  
Author(s):  
Inger van Steenoven ◽  
Barbara Noli ◽  
Cristina Cocco ◽  
Gian-Luca Ferri ◽  
Patrick Oeckl ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Analytical Methods ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Disease Stage ◽  
Selected Reaction Monitoring ◽  
Csf Biomarkers ◽  
Potential Biomarker ◽  
Proteomic Study

In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer’s disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM). We further addressed associations of VGF with other CSF biomarkers and cognition. VGF levels were lower in CSF from patients with DLB compared to either AD patients or controls. VGF was positively correlated with CSF tau and α-synuclein (0.55 < r < 0.75), but not with Aβ1-42. In DLB patients, low VGF levels were related to a more advanced cognitive decline at time of first presentation, whereas high levels of VGF were associated with steeper subsequent longitudinal cognitive decline. Hence, CSF VGF levels were lower in DLB compared to both AD and controls across different analytical methods. The strong associations with cognitive decline further points out VGF as a possible disease stage or prognostic marker for DLB.

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