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Testing the link be...
Testing the link between isoaspartate and Alzheimer's disease etiology
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- Wang, Jijing (author)
- Karolinska Inst, Dept Med Biophys & Biochem, 9A Tomtebodavagen 16, S-17165 Stockholm, Sweden.
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- Guo, Cong (author)
- Shanghai Univ, Coll Sci, Dept Phys, Shanghai, Peoples R China.;Shanghai Univ, Coll Sci, Int Ctr Quantum & Mol Struct, Shanghai, Peoples R China.
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- Meng, Zhaowei (author)
- Karolinska Inst, Dept Med Biophys & Biochem, 9A Tomtebodavagen 16, S-17165 Stockholm, Sweden.
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- Zwan, Marissa D. (author)
- Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Neurochem Lab,Dept Clin Chem, Amsterdam, Netherlands.
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- Chen, Xin (author)
- Shanghai Univ, Coll Sci, Dept Phys, Shanghai, Peoples R China.;Shanghai Univ, Coll Sci, Int Ctr Quantum & Mol Struct, Shanghai, Peoples R China.
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- Seelow, Sven (author)
- Karolinska Institutet
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- Lundström, Susanna L. (author)
- Karolinska Inst, Dept Med Biophys & Biochem, 9A Tomtebodavagen 16, S-17165 Stockholm, Sweden.
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- Rodin, Sergey (author)
- Uppsala universitet,Thoraxkirurgi,Karolinska Inst, Dept Med Biophys & Biochem, 9A Tomtebodavagen 16, S-17165 Stockholm, Sweden.
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- Teunissen, Charlotte E. (author)
- Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Neurochem Lab,Dept Clin Chem, Amsterdam, Netherlands.
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- Zubarev, Roman A. (author)
- Karolinska Institutet
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Karolinska Inst, Dept Med Biophys & Biochem, 9A Tomtebodavagen 16, S-17165 Stockholm, Sweden Shanghai Univ, Coll Sci, Dept Phys, Shanghai, Peoples R China.;Shanghai Univ, Coll Sci, Int Ctr Quantum & Mol Struct, Shanghai, Peoples R China. (creator_code:org_t)
- 2022-08-04
- 2023
- English.
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In: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 19:4, s. 1491-1502
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Abstract
Subject headings
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- Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins as a result of spontaneous deamidation. IsoAsp disrupts protein structures, making them prone to aggregation. Here we strengthened the link between isoAsp and Alzheimer's disease (AD) by novel approaches to isoAsp analysis in human serum albumin (HSA), the most abundant blood protein and a major carrier of amyloid beta (A beta) and phosphorylated tau (p-tau) in blood. We discovered a reduced amount of anti-isoAsp antibodies (P < 0.0001), an elevated isoAsp level in HSA (P < 0.001), more HSA aggregates (P < 0.0001), and increased levels of free A beta (P < 0.01) in AD blood compared to controls. We also found that deamidation significantly reduces HSA capacity to bind with A beta and p-tau (P < 0.05). These suggest the presence in AD of a bottleneck in clearance of A beta and p-tau, leading to their increased concentrations in the brain and facilitating their aggregations there.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- aging
- Alzheimer's disease (AD)
- blood analysis
- deamidation
- enzyme-linked immunosorbent assay (ELISA)
- human serum albumin (HSA)
- in vitro diagnostics
- mass spectrometry
- protein aggregation
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Wang, Jijing
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Guo, Cong
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Meng, Zhaowei
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Zwan, Marissa D.
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Chen, Xin
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Seelow, Sven
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Lundström, Susan ...
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Rodin, Sergey
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Teunissen, Charl ...
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Zubarev, Roman A ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medicinal Chemis ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Clinical Laborat ...
- Articles in the publication
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Alzheimer's & De ...
- By the university
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Uppsala University
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Karolinska Institutet