Cross-Sectional Characterization of Albumin Glycation State in Cerebrospinal Fluid and Plasma From Alzheimer’s Disease Patients

Costa, Montserrat; Mestre, Anna; Horrillo, Raquel; Ortiz, Ana M.; Pérez, Alba; Ruiz, Agustín; Boada, Merçé; Grancha, Salvador

doi:10.14283/jpad.2018.48

Cited by 5 publications

(9 citation statements)

References 27 publications

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“…Moreover, a different pattern of glycated isoforms was also observed in both plasma and CSF of AD patients in comparison to healthy controls, with a higher content of both oxidized + glycated and cysteinylated + glycated isoforms. Furthermore, when comparing albumin glycation in plasma and CSF samples obtained from the same patients, AD patients showed to have higher glycation of albumin in plasma than in CSF [124]. These data support the role of glycation and oxidative stress in AD and deserve further investigation.…”

Section: Emerging Insights On Albumin In Adsupporting

confidence: 58%

“…In relation to albumin glycation, plasma albumin has been found to be more glycated in AD patients than in healthy controls [124]. Moreover, a different pattern of glycated isoforms was also observed in both plasma and CSF of AD patients in comparison to healthy controls, with a higher content of both oxidized + glycated and cysteinylated + glycated isoforms.…”

Section: Emerging Insights On Albumin In Admentioning

confidence: 95%

“…Recently, post-translational modifications of albumin (oxidation and glycation) have been compared in plasma and CSF samples from mildmoderate AD patients and healthy age-matched donors [123,124]. Regarding oxidation, levels of reduced albumin in the plasma and CSF of AD patients were lower than in healthy controls supporting the hypothesis that the albumin of AD patients was significantly more oxidized than albumin in healthy subjects.…”

Section: Emerging Insights On Albumin In Admentioning

confidence: 98%

“…This product retains its Aβ binding capacity and has no quantifiable levels of Aβ [139]. In addition to this effect on Aβ, based on recent investigations [122][123][124] plasma exchange also removes a portion of the patient's "old" and less-functional albumin (i.e. oxidized and glycated) which is replaced with "new" fresh therapeutic albumin.…”

Section: Clinical Trials On Plasma Exchange With Albumin Replacement In Admentioning

confidence: 99%

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Emerging insights into the role of albumin with plasma exchange in Alzheimer’s disease management

Costa

Páez

2021

Transfusion and Apheresis Science

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Alzheimer's disease (AD) is a neurodegenerative process that inexorably leads to progressive deterioration of cognition function and, ultimately, death. Central pathophysiologic features of AD include the accumulation of extracellular plaques comprised of amyloid-β peptide (Aβ) and the presence of intraneuronal neurofibrillary tangles. However, a large body of evidence suggests that oxidative stress and inflammation are major contributors to the pathogenesis and progression of AD. To date, available pharmacologic treatments are only symptomatic. Clinical trials focused on amyloid and non-amyloid-targeted treatments with small molecule pharmacotherapy and immunotherapies have accumulated a long list of failures. Considering that around 90 % of the circulating Aβ is bound to albumin, and that a dynamic equilibrium exists between peripheral and central Aβ, plasma exchange with albumin replacement has emerged as a new approach in a multitargeted AD therapeutic strategy (AMBAR Program). In plasma exchange, a patient's plasma is removed by plasmapheresis to eliminate toxic endogenous substances, including Aβ and functionally impaired albumin. The fluid replacement used is therapeutic albumin, which acts not only as a plasma volume expander but also has numerous pleiotropic functions (e.g., circulating Aβ-binding capacity, transporter, detoxifier, antioxidant) that are clinically relevant for the treatment of AD. Positive results from the AMBAR Program (phase 1, 2, an 2b/3 trials), i.e., slower decline or stabilization of disease symptoms in the most relevant clinical efficacy and safety endpoints, offer a glimmer of hope to both AD patients and caregivers.

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Section: Emerging Insights On Albumin In Adsupporting

confidence: 58%

Section: Emerging Insights On Albumin In Admentioning

confidence: 95%

Section: Emerging Insights On Albumin In Admentioning

confidence: 98%

Section: Clinical Trials On Plasma Exchange With Albumin Replacement In Admentioning

confidence: 99%

See 2 more Smart Citations

Emerging insights into the role of albumin with plasma exchange in Alzheimer’s disease management

Costa

Páez

2021

Transfusion and Apheresis Science

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“…To A series of basic research studies have been carried out in plasma and CSF samples from patients in the phase 2 trial [48], to characterize albumin PTMs such as oxidation and early glycation occurring in AD patients as compared to healthy age-matched controls [49,50].…”

Section: Article Highlightsmentioning

confidence: 99%

Therapeutic plasma exchange with albumin: a new approach to treat Alzheimer’s disease

Boada

Martínez-Lage

Serrano-Castro

et al. 2021

Expert Review of Neurotherapeutics

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Introduction: Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most common cause of dementia. It has a complex pathophysiology that is not yet completely understood, where multiple central, systemic, and environmental factors play a key role in disease progression. Understanding the multifactorial nature of AD is paramount to formulate new therapies. Areas covered: The authors reviewed the role of the amyloid-β-binding, antioxidant, and immunomodulatory properties of albumin in AD and the use of therapeutic plasma exchange (PE) in neurology. The results from the Alzheimer Management By Albumin Replacement (AMBAR) trial that combined the use of PE with albumin replacement in patients with mild-to-moderate AD, are also analyzed. Expert opinion: Findings from the AMBAR study provide encouraging results in the treatment of AD with PE and albumin replacement, especially in patients at the moderate stage of the disease, who showed less cognitive decline from baseline compared with placebo in most of the variables analyzed. Further research is warranted to ascertain the possible mechanisms of action underlying these results. Different cohorts of patients that may also benefit from this treatment, such as those with mild cognitive impairment or other types of dementia, could also be the target of additional studies.

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TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation

Martí-Andrés,

Finamor,

Torres-Cuevas

et al. 2024

EMBO J

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It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans.

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Cross-Sectional Characterization of Albumin Glycation State in Cerebrospinal Fluid and Plasma From Alzheimer’s Disease Patients

Cited by 5 publications

References 27 publications

Emerging insights into the role of albumin with plasma exchange in Alzheimer’s disease management

Emerging insights into the role of albumin with plasma exchange in Alzheimer’s disease management

Therapeutic plasma exchange with albumin: a new approach to treat Alzheimer’s disease

TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation

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