Serum Albumin Concentration and Cognitive Impairment

Llewellyn, David J.

doi:10.2174/1567209197471562050

Cited by 15 publications

(18 citation statements)

References 26 publications

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“…Regarding nutrition, many reports have shown that hypoalbuminemia is associated with cognitive dysfunction . From the preventive perspective, albumin has been reported to have an anti‐oxidant effect, mitigating toxicity and inhibiting the formation of amyloid β peptide fibrils.…”

Section: Introductionmentioning

confidence: 99%

Serum albumin/globulin ratio is associated with cognitive function in community‐dwelling older people: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study

Maeda

Takeya

Oguro

et al. 2019

Geriatrics Gerontology Int

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Aim The objective of this study was to clarify the relationship between cognitive function and the serum albumin/globulin ratio (A/G ratio) in community‐dwelling Japanese older adults. Methods Randomly extracted residents in both urban and rural parts of Japan were enrolled in this study. A total of 1827 participants with a mean age of 70 or 80 years were recruited. A venue survey method was carried out with comprehensive studies, including interviews, blood collection, physical examination and cognitive function tests. Results Univariate analysis showed a significant positive correlation between the total Japanese version of the Montreal Cognitive Assessment score and the serum A/G ratio at the age of 70 and 80 years, in which better cognitive function was associated with a high serum A/G ratio. Multiple regression analysis with the total Japanese version of the Montreal Cognitive Assessment score as the dependent variable showed that the serum albumin level, serum globulin level, serum A/G ratio, C‐reactive protein, years of formal education and sex were related to the Japanese version of the Montreal Cognitive Assessment total score at the age of 70 years, and that the serum albumin level, serum globulin level, serum A/G ratio, C‐reactive protein, years of formal education and stroke were related at the age of 80 years. The serum A/G ratio showed a better correlation than the serum globulin levels at the age of 70 and 80 years (70 years: β = 0.131 vs –0.111, 80 years: β = 0.108 vs –0.071). Conclusions We found a correlation between cognitive function and the serum A/G ratio in community‐dwelling older people, suggesting that nutritional status and chronic inflammation might influence cognitive function. Geriatr Gerontol Int 2019; 19: 967–971.

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Section: Introductionmentioning

confidence: 99%

Serum albumin/globulin ratio is associated with cognitive function in community‐dwelling older people: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study

Maeda

Takeya

Oguro

et al. 2019

Geriatrics Gerontology Int

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“…Therefore, it is likely that plasma protein dysfunctions affect the clearance of Ab from the CNS and consequently Ab plaque deposition within the brain. For instance, recent clinical studies show that low albumin levels are associated with increased odds of cognitive impairment and, moreover, indicate the use of albumin in plasma exchange therapies as a promising avenue in the treatment of mild to moderate Alzheimer's disease (2,3). Furthermore, HSA is also an effective inhibitor of Ab fibrilization (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Stoichiometry and Affinity of the Human Serum Albumin-Alzheimer's Aβ Peptide Interactions

Milojevic

Melacini

2011

Biophysical Journal

107

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A promising strategy to control the aggregation of the Alzheimer's Aβ peptide in the brain is the clearance of Aβ from the central nervous system into the peripheral blood plasma. Among plasma proteins, human serum albumin plays a critical role in the Aβ clearance to the peripheral sink by binding to Aβ oligomers and preventing further growth into fibrils. However, the stoichiometry and the affinities of the albumin-Aβ oligomer interactions are still to be fully characterized. For this purpose, here we investigate the Aβ oligomer-albumin complexes through a novel and generally applicable experimental strategy combining saturation transfer and off-resonance relaxation NMR experiments with ultrafiltration, domain deletions, and dynamic light scattering. Our results show that the Aβ oligomers are recognized by albumin through sites that are evenly partitioned across the three albumin domains and that bind the Aβ oligomers with similar dissociation constants in the 1-100 nM range, as assessed based on a Scatchard-like model of the albumin inhibition isotherms. Our data not only explain why albumin is able to inhibit amyloid formation at physiological nM Aβ concentrations, but are also consistent with the presence of a single high affinity albumin-binding site per Aβ protofibril, which avoids the formation of extended insoluble aggregates.

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“…The inhibition of A␤ self-association by HSA has both pathological implications and therapeutic potential (4 -7). Low serum albumin concentrations have been reported to be associated with increased cognitive impairment in elderly patients (4), and plasmapheresis with therapeutic albumin is currently being assessed in clinical trials as a potential treatment for mild to moderate Alzheimer's disease (8,9). The pathological and therapeutic potential of HSA warrants a comprehensive understanding of the molecular mechanism underlying the HSA-A␤ interactions, not only to improve the HSA therapeutic efficiency but also to elucidate basic principles of amyloid inhibition that will facilitate the design of new amyloid inhibitors (10 -17).…”

mentioning

confidence: 99%

Atomic-resolution map of the interactions between an amyloid inhibitor protein and amyloid β (Aβ) peptides in the monomer and protofibril states

Algamal¹,

Ahmed

Jafari³

et al. 2017

Journal of Biological Chemistry

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Self-association of amyloid β (Aβ) peptides is a hallmark of Alzheimer's disease and serves as a general prototype for amyloid formation. A key endogenous inhibitor of Aβ self-association is human serum albumin (HSA), which binds ∼90% of plasma Aβ. However, the exact molecular mechanism by which HSA binds Aβ monomers and protofibrils is not fully understood. Here, using dark-state exchange saturation transfer NMR and relaxation experiments complemented by morphological characterization, we mapped the HSA-Aβ interactions at atomic resolution by examining the effects of HSA on Aβ monomers and soluble high-molecular weight oligomeric protofibrils. We found that HSA binds both monomeric and protofibrillar Aβ, but the affinity of HSA for Aβ monomers is lower than for Aβ protofibrils ( values are submillimolar rather than micromolar) yet physiologically relevant because of the ∼0.6-0.7 mm plasma HSA concentration. In both Aβ protofibrils and monomers, HSA targets key Aβ self-recognition sites spanning the β strands found in cross-β protofibril structures, leading to a net switch from direct to tethered contacts between the monomeric Aβ and the protofibril surface. These HSA-Aβ interactions are isoform-specific, because the HSA affinity of Aβ monomers is lower for Aβ(1-42) than for Aβ(1-40). In addition, the HSA-induced perturbations of the monomer/protofibrils pseudo-equilibrium extend to the C-terminal residues in the Aβ(1-42) isoform but not in Aβ(1-40). These results provide an unprecedented view of how albumin interacts with Aβ and illustrate the potential of dark-state exchange saturation transfer NMR in mapping the interactions between amyloid-inhibitory proteins and amyloidogenic peptides.

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Serum Albumin Concentration and Cognitive Impairment

Cited by 15 publications

References 26 publications

Serum albumin/globulin ratio is associated with cognitive function in community‐dwelling older people: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study

Serum albumin/globulin ratio is associated with cognitive function in community‐dwelling older people: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study

Stoichiometry and Affinity of the Human Serum Albumin-Alzheimer's Aβ Peptide Interactions

Atomic-resolution map of the interactions between an amyloid inhibitor protein and amyloid β (Aβ) peptides in the monomer and protofibril states

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