From corpora amylacea to wasteosomes: History and perspectives

Riba, Marta; Valle, Jaume del; Augé, Elisabet; Vilaplana, Jordi; Pelegrı́, Carme

doi:10.1016/j.arr.2021.101484

Cited by 30 publications

(55 citation statements)

References 90 publications

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“…Beyond tau, CA are likely responsive to other perturbations within the brain, likely acting generally to eliminate aggregated proteins, damaged organelles and other factors [4,18], and possibly microbial elements [18,56], implying broad relevance to neurological diseases [1,14,57,58]. Indeed, CA accumulation or a related process, astrocytic clasmatodendrosis, may occur in brains from younger patients exposed to drug-induced stress [54,55].…”

Section: Discussionmentioning

confidence: 99%

“…Corpora amylacea (CA) are spherical structures ranging from approximately 10 to 50 µm in diameter that are present in the central nervous system [1][2][3] and other tissues (e.g., liver, prostate, skeletal muscle) where they serve as putative waste disposal sites referred to as wasteosomes [4]. CA are densely packed and organized in a concentric ring structure, primarily composed of carbohydrates [5], but can contain cellular macromolecules, proteins, and even organelles within this dense matrix, [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease

Wander

Tsujimoto

Ervin

et al. 2022

acta neuropathol commun

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Corpora amylacea (CA) and their murine analogs, periodic acid Schiff (PAS) granules, are age-related, carbohydrate-rich structures that serve as waste repositories for aggregated proteins, damaged cellular organelles, and other cellular debris. The structure, morphology, and suspected functions of CA in the brain imply disease relevance. Despite this, the link between CA and age-related neurodegenerative diseases, particularly Alzheimer’s disease (AD), remains poorly defined. We performed a neuropathological analysis of mouse PAS granules and human CA and correlated these findings with AD progression. Increased PAS granule density was observed in symptomatic tau transgenic mice and APOE knock-in mice. Using a cohort of postmortem AD brain samples, we examined CA in cognitively normal and dementia patients across Braak stages with varying APOE status. We identified a Braak-stage dependent bimodal distribution of CA in the dentate gyrus, with CA accumulating and peaking by Braak stages II–III, then steadily declining with increasing tau burden. Refined analysis revealed an association of CA levels with both cognition and APOE status. Finally, tau was detected in whole CA present in human patient cerebrospinal fluid, highlighting CA-tau as a plausible prodromal AD biomarker. Our study connects hallmarks of the aging brain with the emergence of AD pathology and suggests that CA may act as a compensatory factor that becomes depleted with advancing tau burden.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease

Wander

Tsujimoto

Ervin

et al. 2022

acta neuropathol commun

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“…Therefore, glial cells, by losing their homeostatic functions, may contribute to the neurodegeneration and epilepsy occurring in LD. On the other hand, the observation—in line with what occurs in normal aging and in other neurodegenerative diseases [ 132 ]—that astrocytes in LD accumulate CALs [ 38 , 39 , 51 ] (also termed “wasteosomes”) [ 132 , 133 ], supports the suggestion that they may be waste containers that are produced to clean up the brain [ 132 , 133 ]. It is thought that they may be secreted by the cells [ 38 , 71 ] and eliminated by macrophagic phagocytosis once they reach the cervical lymph nodes through the meningeal lymphatic system [ 134 ].…”

Section: Discussionmentioning

confidence: 61%

Glial Contributions to Lafora Disease: A Systematic Review

2022

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Background: Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and molecular alterations, neuroinflammation has emerged as another key histopathological feature of LD. Methods: To investigate the role of astrocytes and microglia in LD, we performed a systematic review according to the PRISMA statement. PubMed, Scopus, and Web-of-Science database searches were performed independently by two reviewers. Results: Thirty-five studies analyzing the relationship of astrocytes and microglia with LD and/or the effects of anti-inflammatory treatments in LD animal models were identified and included in the review. Although LD has long been dominated by a neuronocentric view, a growing body of evidence suggests a role of glial cells in the disease, starting with the finding that these cells accumulate PBs. We discuss the potential meaning of glial PB accumulations, the likely factors activating glial cells, and the possible contribution of glial cells to LD neurodegeneration and epilepsy. Conclusions: Given the evidence for the role of neuroinflammation in LD, future studies should consider glial cells as a potential therapeutic target for modifying/delaying LD progression; however, it should be kept in mind that these cells can potentially assume multiple reactive phenotypes, which could influence the therapeutic response.

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“…In the pathological description, we also included the presence of alterations in the distribution of granule cells in the DG (dispersion, bi-layer pattern or patchy alterations), and the presence of corpora amylacea (spherical polyglucosan bodies with a diameter of around 10-15 µm) that are found mostly in the periventricular and subpial regions of the human brain during normal aging. Although the pathological significance of corpora amylacea is not yet clear, they are frequently described in some neurodegenerative diseases and also associated with TLE, particularly with hippocampal sclerosis (e.g., see Rohn, 2015;Riba et al, 2019Riba et al, , 2021.…”

Section: Histopathological Analysismentioning

confidence: 99%

Neuroanatomical and psychological considerations in temporal lobe epilepsy

et al. 2022

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Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is associated with a variety of structural and psychological alterations. Recently, there has been renewed interest in using brain tissue resected during epilepsy surgery, in particular ‘non-epileptic’ brain samples with normal histology that can be found alongside epileptic tissue in the same epileptic patients — with the aim being to study the normal human brain organization using a variety of methods. An important limitation is that different medical characteristics of the patients may modify the brain tissue. Thus, to better determine how ‘normal’ the resected tissue is, it is fundamental to know certain clinical, anatomical and psychological characteristics of the patients. Unfortunately, this information is frequently not fully available for the patient from which the resected tissue has been obtained — or is not fully appreciated by the neuroscientists analyzing the brain samples, who are not necessarily experts in epilepsy. In order to present the full picture of TLE in a way that would be accessible to multiple communities (e.g., basic researchers in neuroscience, neurologists, neurosurgeons and psychologists), we have reviewed 34 TLE patients, who were selected due to the availability of detailed clinical, anatomical, and psychological information for each of the patients. Our aim was to convey the full complexity of the disorder, its putative anatomical substrates, and the wide range of individual variability, with a view toward: (1) emphasizing the importance of considering critical patient information when using brain samples for basic research and (2) gaining a better understanding of normal and abnormal brain functioning. In agreement with a large number of previous reports, this study (1) reinforces the notion of substantial individual variability among epileptic patients, and (2) highlights the common but overlooked psychopathological alterations that occur even in patients who become “seizure-free” after surgery. The first point is based on pre- and post-surgical comparisons of patients with hippocampal sclerosis and patients with normal-looking hippocampus in neuropsychological evaluations. The second emerges from our extensive battery of personality and projective tests, in a two-way comparison of these two types of patients with regard to pre- and post-surgical performance.

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From corpora amylacea to wasteosomes: History and perspectives

Cited by 30 publications

References 90 publications

Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease

Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease

Glial Contributions to Lafora Disease: A Systematic Review

Neuroanatomical and psychological considerations in temporal lobe epilepsy

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