Cerebrospinal fluid β-amyloid1–42 levels in the differential diagnosis of Alzheimer’s Disease – systematic review and meta-analysis

Mo, JinA; Lim, Ju Hee

doi:10.5176/2382-607x_arp14.12

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…Moreover, MgT treatment restored the CSF Aβ 1–42 levels in the APP/PS1 mice. These observations are in line with studies suggesting that reduced CSF Aβ 1–42 levels are a potential biomarker for the diagnosis of AD (35). We were interested to observe that the expression of APH‐1α/‐1 b was up‐regulated when we injected the CSF of APP/PS1 mice into WT mice intracerebroventricularly, and this up‐regulation was blocked by the addition of Aβ antibodies.…”

Section: Discussionsupporting

confidence: 91%

By suppressing the expression of anterior pharynx‐defective‐1α and ‐1β and inhibiting the aggregation of β‐amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice

Guan

Guo

et al. 2015

FASEB j.

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Alzheimer's disease (AD) is associated with a magnesium ion (Mg 2+ ) deficit in the serum or brain. However, the mechanisms regulating the roles of Mg 2+ in the pathologic condition of AD remain unknown. We studied whether brain Mg 2+ can decrease b-amyloid (Ab) deposition and ameliorate the cognitive decline in a model of AD, the APPswe/PS1DE9 transgenic (Tg) mouse. We used a recently developed compound, magnesium-L-threonate (MgT), for a treatment that resulted in enhanced clearance of Ab in an anterior pharynx-defective (APH)-1a/-1b-dependent manner. To further explore how MgT treatment inhibits cognitive decline in APP/PS1 Tg mice, the critical molecules for amyloid precursor protein (APP) cleavage and signaling pathways were investigated. In neurons, ERK1/2 and PPARg signaling pathways were activated by MgT treatment, which in turn suppressed (by >80%) the expression of APH-1a/-1b, which is responsible for the deposition of Ab and potentially contributes to the memory deficit that occurs in AD. More important, Ab oligomers in the cerebrospinal fluid (CSF) further promoted the expression of APH-1a/-1b (by >2.5-fold), which enhances the g-cleavage of APP and Ab deposition during AD progression. These findings provide new insights into the mechanisms of AD progression and are instrumental for developing better strategies to combat the disease.-Yu, X., Guan, P.-P., Guo, J.-W., Wang, Y., Cao, L.-L., Xu, G.-B., Konstantopoulos, K., Wang, Z.-Y., Wang, P. By suppressing the expression of anterior pharynxdefective-1a and -1b and inhibiting the aggregation of b-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice. FASEB J. 29, 5044-5058 (2015). www.fasebj.orgAlzheimer's disease (AD) is usually characterized by cognitive decline and dementia in aged people. Clinically, it is diagnosed by the accumulation of b-amyloid (Ab) protein in amyloid plaques (APs) and the hyperphosphorylation of tau in neurofibrillary tangles (NFTs) (1). Although the mechanisms of Ab deposition and tau phosphorylation have not been thoroughly delineated, recent reports have revealed that Mg 2+ elevation may be involved in Ab clearance (2). These observations are based on prior studies that suggested that brain magnesium ion (Mg 2+ ) levels (3) and serum Mg 2+ concentration (4) are significantly lower in patients with AD than in age-matched normal subjects. In light of these studies, dyshomeostasis of Mg 2+ in the brain may be involved in the pathogenesis and progression of AD.Although the mechanisms that regulate Mg 2+ concentrations over the course of the development of AD have yet to be defined, the potential roles of Mg 2+ in AD have been examined in a few investigations. For example, it has been shown that a reduced level of Mg 2+ blocks the NMDA receptor (NMDAR)-mediated Ca 2+ influx that is essential for associative learning and long-term memory formation in Drosophila (5). The administration of magnesium-L-threonate (MgT) to aged rats increases Mg 2+ levels in the...

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Section: Discussionsupporting

confidence: 91%

By suppressing the expression of anterior pharynx‐defective‐1α and ‐1β and inhibiting the aggregation of β‐amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice

Guan

Guo

et al. 2015

FASEB j.

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“…Further to preanalytical factors, concentrations of CSF Aβ also vary between individuals [33]; thus, individuals with constitutively high or low quantities of Aβ 42 relative to chosen diagnostic “cut points” may be vulnerable to misinterpretation of test results. Recent meta‐analysis shows that when comparing AD versus nondemented controls and non‐AD dementias, CSF Aβ 42 has a pooled sensitivity of 0.80 (95% confidence interval = 0.78–0.82) and a pooled specificity of 0.76 (95% confidence interval = 0.74–0.78) [34]. Increasingly, reports suggest improved diagnostic and mild cognitive impairment–AD conversion predictive power when Aβ 42 is considered in ratio to Aβ 40 [1,15,16,31,35,36].…”

Section: Introductionmentioning

confidence: 99%

Amyloid β peptides are differentially vulnerable to preanalytical surface exposure, an effect incompletely mitigated by the use of ratios

Toombs

Foiani

Wellington

et al. 2018

Alz & Dem Diag Ass & Dis Mo

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Introduction We tested the hypothesis that the amyloid β (Aβ) peptide ratios are more stable than Aβ 42 alone when biofluids are exposed to two preanalytical conditions known to modify measurable Aβ concentration. Methods Human cerebrospinal fluid (CSF) and culture media (CM) from human cortical neurons were exposed to a series of volumes and polypropylene surfaces. Aβ 42 , Aβ 40 , and Aβ 38 peptide concentrations were measured using a multiplexed electrochemiluminescence immunoassay. Data were analyzed using mixed models in R. Results Decrease of measurable Aβ peptide concentrations was exaggerated in longer peptides, affecting the Aβ 42 :Aβ 40 and Aβ 42 :Aβ 38 ratios. However, the effect size of surface treatment was reduced in Aβ peptide ratios versus Aβ 42 alone. For Aβ 42 :Aβ 40 , the effect was reduced by approximately 50% (volume) and 75% (transfer) as compared to Aβ 42 alone. Discussion Use of Aβ ratios, in conjunction with concentrations, may mitigate confounding factors and assist the clinical diagnostic process for Alzheimer's disease.

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“…Interestingly, we found a significant effect of tau pathology on the Aβ1-42/Aβ1-40 ratio in the culture medium, with samples containing tangles showing the highest Aβ1-42/Aβ1-40 ratio. More commonly conducted studies examining CSF from human patients have observed an overall decline in Aβ1-42 and Aβ1-42/Aβ1-40 ratio during normal ageing, which is exacerbated by both APOE4 genotype and a diagnosis of AD [16][17][18][19]26,28,85 . Again, the lack of change in Aβ1-42 over time in our sample set differs from this, which may reflect different processes being captured in HBSC medium versus CSF/ISF, or could be due to limits in ELISA sensitivity for Aβ1-42.…”

Section: Discussionmentioning

confidence: 99%

Opposing roles of physiological and pathological amyloid-β on synapses in live human brain slice cultures

McGeachan,

Meftah,

Taylor

et al. 2024

Preprint

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In Alzheimer’s disease, it is theorised that amyloid beta (Aβ) and tau pathology contribute to synapse loss. However, there is limited information on how endogenous levels of tau and Aβ protein relate to patient characteristics, or how manipulating physiological levels of Aβ impacts synapses, in living adult, human brain. Here, we employed live human brain slice cultures as a translational tool to assess endogenous tau and Aβ release, pathology, and response to experimental manipulation. We found that the levels of Aβ1-40and tau detected in the culture medium depend on donor age, and brain region, respectively. Pharmacologically raising physiological Aβ concentration enhanced levels of synaptic transcripts. Treatment of slices with Aβ-containing Alzheimer’s disease brain extract resulted in postsynaptic Aβ uptake and loss of presynaptic puncta. These data indicate that physiological and pathological Aβ can have opposing effects on synapses in living human brain tissue.

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Cerebrospinal fluid β-amyloid1–42 levels in the differential diagnosis of Alzheimer’s Disease – systematic review and meta-analysis

Cited by 3 publications

References 15 publications

By suppressing the expression of anterior pharynx‐defective‐1α and ‐1β and inhibiting the aggregation of β‐amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice

By suppressing the expression of anterior pharynx‐defective‐1α and ‐1β and inhibiting the aggregation of β‐amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice

Amyloid β peptides are differentially vulnerable to preanalytical surface exposure, an effect incompletely mitigated by the use of ratios

Opposing roles of physiological and pathological amyloid-β on synapses in live human brain slice cultures

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