Serum Adiponectin and In Vivo Brain Amyloid Deposition in Cognitively Normal Older Adults: A Cohort Study

Kim, Jee Wook

doi:10.14336/ad.2022.1118

Cited by 2 publications

(2 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hormone exerts its actions by binding to specific receptors, namely AdipoR1, AdipoR2, and T-cadherin (CDH13), expressed in various tissues, including the liver, muscle, vascular endothelium, central nervous system, and others [ 3 , 19 , 88 ]. Despite its observed neuroprotective effects in cell-based and animal experiments [ 3 , 18 , 21 , 22 , 23 , 24 , 25 ], the role of adiponectin in the pathogenesis of AD in humans remains controversial, with some studies even suggesting its possible deleterious effects in amyloidogenesis [ 22 , 28 , 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, studies on circulating adiponectin in human subjects have not yielded unanimous results, with the majority of them, including a recent meta-analysis, reporting significantly higher blood adiponectin levels in AD patients compared to participants without cognitive impairment [ 26 , 27 ]. Moreover, recent evidence has indicated that elevated adiponectin might be associated with the severity of Aβ accumulation [ 28 , 29 ], highlighting the potentially detrimental involvement of adiponectin in Aβ amyloidogenesis and neurodegeneration in aging [ 22 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adiponectin Gene Polymorphisms: A Case–Control Study on Their Role in Late-Onset Alzheimer’s Disease Risk

Javor,

Ďurmanová,

Klučková

et al. 2024

Life

View full text Add to dashboard Cite

Adiponectin, a hormone secreted by adipose tissue, plays a complex role in regulating metabolic homeostasis and has also garnered attention for its potential involvement in the pathogenesis of late-onset Alzheimer’s disease (LOAD). The objective of this study was to investigate the association of ADIPOQ variants with plasma adiponectin levels and LOAD risk in subjects from the Slovak Caucasian population. For this purpose, 385 LOAD patients and 533 controls without cognitive impairment were recruited and genotyped for a total of eighteen ADIPOQ single nucleotide polymorphisms (SNPs). Both single-locus and haplotype-based logistic regression analyses were employed to assess the association of SNPs with LOAD risk, while linear regression analysis was used to explore their influence on adiponectin levels in LOAD patients. ADIPOQ variants rs822395 and rs2036373 in intron 1 were found to significantly elevate total adiponectin levels after accounting for several potential confounders. Additional SNPs in the 5′ region and intron 1 exhibited a non-significant trend of association with adiponectin. However, none of the ADIPOQ SNPs showed an association with LOAD risk, neither in the whole-group analysis nor in subgroup analyses after stratification for sex or the APOE ε4 allele, a well-established LOAD risk factor. In summary, while adiponectin has emerged as a potential contributor to the development of LOAD, this study did not unveil any significant involvement of its gene variants in susceptibility to the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adiponectin Gene Polymorphisms: A Case–Control Study on Their Role in Late-Onset Alzheimer’s Disease Risk

Javor,

Ďurmanová,

Klučková

et al. 2024

Life

View full text Add to dashboard Cite

show abstract

Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots

Kell,

Pretorius

2024

Preprint

View full text Add to dashboard Cite

In classical amyloidoses, amyloid fibres form through the nucleation and accretion of protein monomers, with protofibrils and fibrils exhibiting a cross-β motif of parallel or antiparallel β-sheets oriented perpendicular to the fibre direction. These protofibrils and fibrils can intertwine to form mature amyloid fibres. Similar phenomena occur in blood from individuals with circulating inflammatory molecules (also those originating from viruses and bacteria). In the presence of inflammagens, pathological clotting can occur, that results in an anomalous amyloid form termed fibrinaloid microclots. Previous proteomic analyses of these microclots have shown the presence of non-fibrin(ogen) proteins, suggesting a more complex mechanism than simple entrapment. We provide evidence against a simple entrapment model, noting that clot pores are too large and centrifugation would have removed weakly bound proteins. Instead, we explore whether co-aggregation into amyloid fibres may involve axial (multiple proteins within the same fibril), lateral (single-protein fibrils contributing to a fibre), or both types of integration. Our analysis of proteomic data from fibrinaloid microclots in different diseases shows no significant overlap with the normal plasma proteome and no correlation between plasma protein abundance and presence in microclots. Notably, abundant plasma proteins like α-2-macroglobulin, fibronectin, and transthyretin are absent from microclots, while less abundant proteins such as adiponectin, periostin, and von Willebrand Factor are well represented. Using bioinformatic tools including AmyloGram and AnuPP, we found that proteins entrapped in fibrinaloid microclots exhibit high amyloidogenic tendencies, suggesting their integration as cross-β elements into amyloid structures. This integration likely contributes to the microclots’ resistance to proteolysis. Our findings underscore the role of cross-seeding in fibrinaloid microclot formation and highlight the need for further investigation into their structural properties and implications in thrombotic and amyloid diseases. These insights provide a foundation for developing novel diagnostic and therapeutic strategies targeting amyloidogenic cross-seeding in blood clotting disorders.

show abstract

Serum Adiponectin and In Vivo Brain Amyloid Deposition in Cognitively Normal Older Adults: A Cohort Study

Cited by 2 publications

References 72 publications

Adiponectin Gene Polymorphisms: A Case–Control Study on Their Role in Late-Onset Alzheimer’s Disease Risk

Adiponectin Gene Polymorphisms: A Case–Control Study on Their Role in Late-Onset Alzheimer’s Disease Risk

Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots

Contact Info

Product

Resources

About