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Exploring the elusive composition of corpora amylacea of human brain.

ABSTRACT: Corpora amylacea (CA) are polyglucosan bodies that accumulate in the human brain during ageing and are also present in large numbers in neurodegenerative conditions. Theories regarding the function of CA are regularly updated as new components are described. In previous work, we revealed the presence of some neo-epitopes in CA and the existence of some natural IgM antibodies directed against these neo-epitopes. We also noted that these neo-epitopes and IgMs were the cause of false staining in CA immunohistochemical studies, and disproved the proposed presence of ?-amyloid peptides and tau protein in them. Here we extend the list of components erroneously attributed to CA. We show that, contrary to previous descriptions, CA do not contain GFAP, S100, AQP4, NeuN or class III ?-tubulin, and we question the presence of other components. Nonetheless, we observe that CA contains ubiquitin and p62, both of them associated with processes of elimination of waste substances, and also glycogen synthase, an indispensable enzyme for polyglucosan formation. In summary, this study shows that it is imperative to continue reviewing previous studies about CA but, more importantly, it shows that the vision of CA as structures involved in protective or cleaning mechanisms remains the most consistent theory.

SUBMITTER: Auge E

PROVIDER: S-EPMC6131176 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Exploring the elusive composition of corpora amylacea of human brain.

Augé Elisabet E Duran Jordi J Guinovart Joan J JJ Pelegrí Carme C Vilaplana Jordi J

Scientific reports 20180910 1

Corpora amylacea (CA) are polyglucosan bodies that accumulate in the human brain during ageing and are also present in large numbers in neurodegenerative conditions. Theories regarding the function of CA are regularly updated as new components are described. In previous work, we revealed the presence of some neo-epitopes in CA and the existence of some natural IgM antibodies directed against these neo-epitopes. We also noted that these neo-epitopes and IgMs were the cause of false staining in CA ...[more]

PMID: 30202002

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Project description:BackgroundCorpora amylacea of human brain, recently renamed as wasteosomes, are granular structures that appear during aging and also accumulate in specific areas of the brain in neurodegenerative conditions. Acting as waste containers, wasteosomes are formed by polyglucosan aggregates that entrap and isolate toxic and waste substances of different origins. They are expelled from the brain to the cerebrospinal fluid (CSF), and can be phagocytosed by macrophages. In the present study, we analyze the phagocytosis of wasteosomes and the mechanisms involved in this process. Accordingly, we purified wasteosomes from post-mortem extracted human CSF and incubated them with THP-1 macrophages. Immunofluorescence staining and time-lapse recording techniques were performed to evaluate the phagocytosis. We also immunostained human hippocampal sections to study possible interactions between wasteosomes and macrophages at central nervous system interfaces.ResultsWe observed that the wasteosomes obtained from post-mortem extracted CSF are opsonized by MBL and the C3b complement protein. Moreover, we observed that CD206 and CD35 receptors may be involved in the phagocytosis of these wasteosomes by THP-1 macrophages. Once phagocytosed, wasteosomes become degraded and some of the resulting fractions can be exposed on the surface of macrophages and interchanged between different macrophages. However, brain tissue studies show that, in physiological conditions, CD206 but not CD35 receptors may be involved in the phagocytosis of wasteosomes.ConclusionsThe present study indicates that macrophages have the machinery required to process and degrade wasteosomes, and that macrophages can interact in different ways with wasteosomes. In physiological conditions, the main mechanism involve CD206 receptors and M2 macrophages, which trigger the phagocytosis of wasteosomes without inducing inflammatory responses, thus avoiding tissue damage. However, altered wasteosomes like those obtained from post-mortem extracted CSF, which may exhibit waste elements, become opsonized by MBL and C3b, and so CD35 receptors constitute another possible mechanism of phagocytosis, leading in this case to inflammatory responses.

Project description:BackgroundCorpora amylacea are amyloid bodies commonly found adjacent to damaged prostate epithelium. Little is known about their formation or function. The current study sought to characterize corpora amylacea in prostate tissue and to describe their relationship with clinical, histological, molecular, and lifestyle factors, especially with chronic inflammation which is associated with aggressive disease.MethodsWe studied a cohort of 355 men with prostate cancer and tissue specimens from the Health Professionals Follow-Up Study. Pathologists examined H&E slides and undertook a standardized review for histologic data and inflammation. Trained observers counted corpora amylacea within the benign and predominately tumor areas. Immunohistochemistry biomarkers were available from tissue microarrays. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) to assess associations of chronic inflammation, clinical, histological, molecular, and lifestyle factors with the presence of corpora amylacea.ResultsCorpora amylacea were present in benign tissue area for 298 men (84%). Specimens with moderate-to-severe chronic inflammation were more likely to have corpora amylacea in benign regions (OR = 5.4 95%CI 1.9, 15.6). Moreover, corpora amylacea were more common in men with higher body mass index (OR = 1.13 95%CI 1.01, 1.26). In contrast, Gleason grade (OR = 0.4 95%CI 0.2, 0.8), proliferation index (OR = 0.6 95%CI 0.3, 1.2) and the presence of the TMPRSS2:ERG fusion (OR = 0.4 95%CI 0.2, 0.8) were inversely associated with corpora amylacea presence. TURP specimens were less likely to have corpora amylacea than prostatectomy specimens (OR = 0.12 95%CI 0.03, 0.47). Age, PSA, stage, biomarkers of angiogenesis and PTEN, and vasectomy were not significantly associated with corpora amylacea.ConclusionCorpora amylacea were common among men with prostate cancer and were associated with pro-inflammatory factors, some markers of less aggressive disease, and lack of the TMPRSS2:ERG fusion.

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Exploring the elusive composition of corpora amylacea of human brain.

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Exploring the elusive composition of corpora amylacea of human brain.

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