Effects of Anesthetic Isoflurane and Desflurane on Human Cerebrospinal Fluid Aβ and τ Level

Abstract Background: Accumulation of β-amyloid protein (Aβ) and tau protein is the main feature of Alzheimer disease neuropathogenesis. Anesthetic isoflurane, but not desflurane, may increase Aβ levels in vitro and in animals. Therefore, we set out to determine the effects of isoflurane and desflurane on cerebrospinal fluid (CSF) levels of Aβ and tau in humans. Methods: The participants were assigned into spinal anesthesia (N = 35), spinal plus desflurane anesthesia (N = 33), or spinal plus isoflurane anesthesia (N = 38) group by randomization using computer-generated lists. Pre- and postoperative human CSF samples were obtained through an inserted spinal catheter. The levels of Aβ (Aβ40 and Aβ42) and total tau in the CSF were determined. Results: Here, we show that isoflurane, but not desflurane, was associated with an increase in human CSF Aβ40 levels (from 10.90 to 12.41 ng/ml) 24 h after the surgery under anesthesia compared to spinal anesthesia (from 11.59 to 11.08 ng/ml), P = 0.022. Desflurane, but not isoflurane, was associated with a decrease in Aβ42 levels 2 h after the surgery under anesthesia (from 0.39 to 0.35 ng/ml) compared to spinal anesthesia (from 0.43 to 0.44 ng/ml), P = 0.006. Isoflurane and desflurane did not significantly affect the tau levels in human CSF. Conclusions: These studies have established a system to study the effects of anesthetics on human biomarkers associated with Alzheimer disease and cognitive dysfunction. These findings have suggested that isoflurane and desflurane may have different effects on human CSF Aβ levels.

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Comparison of Analytical Platforms for Cerebrospinal Fluid Measures of β-Amyloid 1-42, Total tau, and P-tau181 for Identifying Alzheimer Disease Amyloid Plaque Pathology

Archives of Neurology ◽

10.1001/archneurol.2011.105 ◽

2011 ◽

Vol 68 (9) ◽

pp. 1137 ◽

Cited By ~ 97

Author(s):

Anne M. Fagan

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Amyloid Plaque ◽

Total Tau ◽

Plaque Pathology ◽

Β Amyloid ◽

Analytical Platforms

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Developmental changes of sialylation of soluble β/A4 amyloid protein precursor derivatives in human cerebrospinal fluid

Molecular Brain Research ◽

10.1016/0169-328x(94)90016-7 ◽

1994 ◽

Vol 27 (2) ◽

pp. 320-322

Author(s):

Nobuyuki Sodeyama ◽

Fumiaki Saito ◽

Kayoko Saito ◽

Tadashi Miyatake ◽

Katsuhiko Yanagisawa

Keyword(s):

Cerebrospinal Fluid ◽

Developmental Changes ◽

Amyloid Protein ◽

Protein Precursor ◽

Amyloid Protein Precursor ◽

Human Cerebrospinal Fluid

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Reduction of SorLA/LR11, a Sorting Protein Limiting β-Amyloid Production, in Alzheimer Disease Cerebrospinal Fluid

Archives of Neurology ◽

10.1001/archneurol.2009.22 ◽

2009 ◽

Vol 66 (4) ◽

Cited By ~ 35

Author(s):

Qiu-Lan Ma ◽

Douglas R. Galasko ◽

John M. Ringman ◽

Harry V. Vinters ◽

Steven D. Edland ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Β Amyloid

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THE β AMYLOID PROTEIN PRECURSOR OF ALZHEIMERʼS DISEASE HAS SOLUBLE DERIVATIVES FOUND IN HUMAN BRAIN AND CEREBROSPINAL FLUID

Journal of Neuropathology & Experimental Neurology ◽

10.1097/00005072-198905000-00237 ◽

1989 ◽

Vol 48 (3) ◽

pp. 378

Author(s):

M. R. Palmert ◽

M. B. Podlisny ◽

D. S. Witker ◽

T. Oltersdorf ◽

L. H. Younkin ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Human Brain ◽

Amyloid Protein ◽

Protein Precursor ◽

Amyloid Protein Precursor ◽

Β Amyloid

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Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias

Neurology ◽

10.1212/wnl.0000000000010814 ◽

2020 ◽

Vol 95 (22) ◽

pp. e3026-e3035

Author(s):

Jozef Hanes ◽

Andrej Kovac ◽

Hlin Kvartsberg ◽

Eva Kontsekova ◽

Lubica Fialova ◽

...

Keyword(s):

Alzheimer Disease ◽

Positive Predictive Value ◽

Diagnostic Accuracy ◽

Predictive Value ◽

Healthy Controls ◽

Class Iii ◽

Total Tau ◽

Β Amyloid ◽

Healthy Participants

ObjectiveTo investigate whether tau phosphorylated at Thr217 (p-tau T217) assay in CSF can distinguish patients with Alzheimer disease (AD) from patients with other dementias and healthy controls.MethodsWe developed and validated a novel Simoa immunoassay to detect p-tau T217 in CSF. There was a total of 190 participants from 3 cohorts with AD (n = 77) and other neurodegenerative diseases (n = 69) as well as healthy participants (n = 44).ResultsThe p-tau T217 assay (cutoff 242 pg/mL) identified patients with AD with accuracy of 90%, with 78% positive predictive value (PPV), 97% negative predictive value (NPV), 93% sensitivity, and 88% specificity, compared favorably with p-tau T181 ELISA (52 pg/mL), showing 78% accuracy, 58% PPV, 98% NPV, 71% specificity, and 97% sensitivity. The assay distinguished patients with AD from age-matched healthy controls (cutoff 163 pg/mL, 98% sensitivity, 93% specificity), similarly to p-tau T181 ELISA (cutoff 60 pg/mL, 96% sensitivity, 86% specificity). In patients with AD, we found a strong correlation between p-tau T217 and p-tau T181, total tau and β-amyloid 40, but not β-amyloid 42.ConclusionsThis study demonstrates that p-tau T217 displayed better diagnostic accuracy than p-tau T181. The data suggest that the new p-tau T217 assay has potential as an AD diagnostic test in clinical evaluation.Classification of evidenceThis study provides Class III evidence that a CSF immunoassay for p-tau T217 distinguishes patients with AD from patients with other dementias and healthy controls.

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Human Cerebrospinal Fluid Apolipoprotein E Isoforms are Apparently Inefficient at Complexing with Synthetic Alzheimer’s Amyloid-β Peptide (Aß1−40) in vitro

Molecular Medicine ◽

10.1007/bf03402018 ◽

2002 ◽

Vol 8 (7) ◽

pp. 376-381 ◽

Cited By ~ 3

Author(s):

Zhongmin Zhou ◽

Norman Relkin ◽

Jorge Ghiso ◽

Jonathan D. Smith ◽

Sam Gandy

Keyword(s):

Cerebrospinal Fluid ◽

Apolipoprotein E ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Human Cerebrospinal Fluid

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Dasatinib Cerebrospinal Fluid Concentration and Plasma Pharmacokinetics: Potential for Central Nervous System Prophylaxis In Philadelphia Chromosome-Positive Leukemia

Blood ◽

10.1182/blood.v116.21.1807.1807 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1807-1807

Author(s):

Naoto Takahashi ◽

Masatomo Miura ◽

Stuart Scott ◽

Hirobumi Saitoh ◽

Mutsuhito Motegi ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Conflicts Of Interest ◽

Philadelphia Chromosome ◽

T Test ◽

Lymphoid Leukemia ◽

Csf Levels ◽

Philadelphia Chromosome Positive

Abstract Abstract 1807 Dasatinib (DA) is approved for use in imatinib-resistant or intolerant chronic myeloid leukemia (CML)/Philadelphia-positive acute lymphoid leukemia (Ph+ALL) and may also be useful for central nervous system (CNS) leukemia accompanied with CML/Ph+ALL; however, little is known about the relationship between DA pharmacokinetics and its ability to penetrate the blood-brain barrier. Consequently, we measured DA plasma and cerebrospinal fluid (CSF) levels by high-performance liquid chromatography in 20 samples obtained from 11 DA-treated patients (seven Ph+ALL and four lymphoid crisis CML). DA was detected in 10 CSF samples from five patients who were treated with 100 mg QD of DA (CSF C4h of detectable group; 3.526±2.604 ng/mL, 1.11–7.95 ng/mL), which was above the IC50 level for wild type BCR-ABL positive leukemia cells in vitro (0.8 nM = 0.39 ng/mL). However, DA was not detected in 10 CSF samples from 7 patients (CSF C4h of non-detectable group; <1.0 ng/mL). The concentration ratio of CSF to plasma was 3.90% (0.42-12.23%), which approached previously reported ratios for imatinib. There were significant differences in the AUC0-4 and the plasma C4h between the CSF detectable (D) and non-detectable (ND) patients (AUC0-4: 268.29±92.452 vs. 90.83±76.45, P=0.00019 by Student t-test, Figure 1; plasma C4h: 126.15±62.58 vs. 47.41±50.935, P=0.00637 by Student t-test). Moreover, there were significant correlations between CSF C4h and AUC0-4 (P<0.01, Figure 2) and between CSF C4h and plasma C2h (P<0.001), together suggesting that penetration of DA into the CSF may depend on DA plasma concentration. To investigate any influence of pharmacogenetic variation on CSF penetration, single nucleotide polymorphisms in genes involved in DA pharmacokinetics and transport (ABCB1, ABCG2, SLC22A1, SLC22A3, and CYP3A4/5) were interrogated; however, no significant correlation between CSF levels and genotype were observed. DA has a 325 fold greater potency than imatinib for inhibiting BCR-ABL tyrosine kinase, which undoubtedly influences the efficacy of DA for Philadelphia-chromosome positive CNS leukemia; however, our data suggest that clinical DA blood level monitoring may help estimate the penetration of DA to the CSF. Disclosures: No relevant conflicts of interest to declare.

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