The Cerebrospinal Fluid Amyloid &amp;#946;42/40 Ratio in the Differentiation of Alzheimers Disease from Non-Alzheimers Dementia

Spies, Petra E.; Slats, Diane; Sjögren, Julia; Kremer, Berry; Verhey, Frans R.J.; Rikkert, Marcel G M Olde; Verbeek, Marcel M.

doi:10.2174/156720510791383796

Cited by 114 publications

(44 citation statements)

References 40 publications

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“…Aβ40 and Aβ42 were significantly lower in the EV fraction than in the EV-depleted medium fraction and in the parent cell lysates (Figure 1E). Given that the Aβ42/Aβ40 ratio may be a better predictor of AD than the individual concentrations of Aβ40 and Aβ42, we calculated the Aβ42/Aβ40 ratio 31,32 and found that the Aβ42/Aβ40 ratio in EVs was significantly higher than in EV-depleted medium or cell lysate (Figure 1F). …”

Section: Resultsmentioning

confidence: 99%

Extracellular vesicle-associated Aβ mediates trans-neuronal bioenergetic and Ca2+-handling deficits in Alzheimer’s disease models

et al. 2016

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Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca2+ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of Aβ but have an increased Aβ42/ Aβ40 ratio; the majority of Aβ is located on the surface of the EVs. Impairment of lysosome function results in increased generation of EVs with elevated Aβ42 levels. EVs may mediate transcellular spread of pathogenic Aβ species that impair neuronal Ca2+ handling and mitochondrial function, and may thereby render neurons vulnerable to excitotoxicity.

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Section: Resultsmentioning

confidence: 99%

Extracellular vesicle-associated Aβ mediates trans-neuronal bioenergetic and Ca2+-handling deficits in Alzheimer’s disease models

et al. 2016

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“…While the ratio of Aβ40 to Aβ42 is typically around 5:1 in cerebrospinal fluid of normal individuals (Spies et al, 2010), the insoluble Aβ in AD brain tissue is often predominantly Aβ42 (Gravina et al, 1995). Full structural models for Aβ42 fibrils based on ssNMR data have not yet been published.…”

Section: Molecular Structural Basis For Amyloid Polymorphismmentioning

confidence: 99%

Amyloid Polymorphism: Structural Basis and Neurobiological Relevance

Tycko

2015

Neuron

367

500

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Summary Our understanding of the molecular structures of amyloid fibrils that are associated with neurodegenerative diseases, of mechanisms by which disease-associated peptides and proteins aggregate into fibrils, and of structural properties of aggregation intermediates has advanced considerably in recent years. Detailed molecular structural models for certain fibrils and aggregation intermediates are now available. It is now well established that amyloid fibrils are generally polymorphic at the molecular level, with a given peptide or protein being capable of forming a variety of distinct, self-propagating fibril structures. Recent results from structural studies and from studies involving cell cultures, transgenic animals, and human tissue provide initial evidence that molecular structural variations in amyloid fibrils and related aggregates may correlate with or even produce variations in disease development. This article reviews our current knowledge of the structural and mechanistic aspects of amyloid formation, as well as current evidence for the biological relevance of structural variations.

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“…This can be expressed as the ratio between sAPPβ and sAPPα (sAPPβ/α) and the ratio between the relative expression of the long Aβ species generated by the amyloidogenic pathway (17-42 aa) in relation to the short Aβ species generated by the non-amyloidogenic pathway (13-16 aa). Furthermore, the ratio between cerebrospinal fluid (CSF) Aβ42 and Aβ40 (Aβ42/40) can be regarded as a marker of the total amyloid load in the brain reflected by amyloid positron emission tomography (PET) [18,19,20]. …”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease

Jensen

Portelius

Siersma

et al. 2016

Dement Geriatr Cogn Disord

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Background: Physical exercise may have some effect on cognition in patients with Alzheimer disease (AD). However, the underlying biochemical effects are unclear. Animal studies have shown that amyloid beta (Aβ), one of the pathological hallmarks of AD, can be altered with high levels of physical activity. Aim: The objective of this study was to elucidate the effect of 16 weeks of moderate- to high-intensity physical exercise on the biomarkers of AD, with special emphasis on the amyloidogenic pathway. Methods: From a total of 53 patients with AD participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study we analyzed cerebrospinal fluid samples for Aβ species, total tau (t-tau), phosphorylated tau (p-tau) and soluble amyloid precursor protein (sAPP) species. We also assessed the patients for apolipoprotein E ε4 (ApoE ε4) genotype. Results: We found no effect of 16 weeks of physical exercise on the selected biomarkers, and no effect of ApoE ε4 genotype. Conclusion: Our findings suggest that the possible effect of physical exercise on cognition in patients with AD is not due to modulation of Aβ, t-tau, p-tau and sAPP species.

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The Cerebrospinal Fluid Amyloid β42/40 Ratio in the Differentiation of Alzheimers Disease from Non-Alzheimers Dementia

Cited by 114 publications

References 40 publications

Extracellular vesicle-associated Aβ mediates trans-neuronal bioenergetic and Ca2+-handling deficits in Alzheimer’s disease models

Extracellular vesicle-associated Aβ mediates trans-neuronal bioenergetic and Ca2+-handling deficits in Alzheimer’s disease models

Amyloid Polymorphism: Structural Basis and Neurobiological Relevance

Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease

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