Quantitative analysis of size and regional distribution of corpora amylacea in the hippocampal formation of obstructive sleep apnoea patients

Xu, Cuicui; Owen, Jessica E.; Gíslason, Þórarinn; Benediktsdóttir, Bryndís; Robinson, Stephen R.

doi:10.1038/s41598-021-99795-8

Cited by 8 publications

(11 citation statements)

References 38 publications

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“…Like PAS granules, CA formation is thought to be central to astrocytes, a prominent cell type in pial and subpial zones proximal to the glia limitans [ 16 , 59 ], where we note the accumulation of AT8 + structures in late-stage AD patients (Fig. 4 A and Table 4 ).…”

Section: Discussionmentioning

confidence: 65%

“…Indeed, CA accumulation or a related process, astrocytic clasmatodendrosis, may occur in brains from younger patients exposed to drug-induced stress [54,55]. Like PAS granules, CA formation is thought to be central to astrocytes, a prominent cell type in pial and subpial zones proximal to the glia limitans [16,59], where we note the accumulation of AT8 + structures in late-stage AD patients (Fig. 4A and Table 4).…”

Section: Discussionmentioning

confidence: 73%

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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: 65%

Section: Discussionmentioning

confidence: 73%

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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“…Few studies have performed a quantitative analysis of CA across hippocampal regions. One study by Xu et al (2021) investigated CA distribution in sleep apnea patients and found CA were most abundant in periventricular regions (alveus, wall of lateral ventricle, fimbria) and undetectable in the CA2 region. Xu et al (2021) found few CA in the CA1 and CA3 regions.…”

Section: Discussionmentioning

confidence: 99%

“…One study by Xu et al (2021) investigated CA distribution in sleep apnea patients and found CA were most abundant in periventricular regions (alveus, wall of lateral ventricle, fimbria) and undetectable in the CA2 region. Xu et al (2021) found few CA in the CA1 and CA3 regions. In our study, CA3 exhibited a higher area occupied by CA than CA1.…”

Section: Discussionmentioning

confidence: 99%

Corpora amylacea negatively correlate with hippocampal tau pathology in Alzheimer’s disease

Dallmeier,

Gober,

Vontell

et al. 2024

Front. Neurosci.

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IntroductionSeverity and distribution of aggregated tau and neurofibrillary tangles (NFT) are strongly correlated with the clinical presentation of Alzheimer’s disease (AD). Clearance of aggregated tau could decrease the rate of NFT formation and delay AD onset. Recent studies implicate corpora amylacea (CA) as a regulator of onset or accumulation of tau pathology. Normally, CA clear brain waste products by amassing cellular debris, which are then extruded into the cerebrospinal fluid to be phagocytosed. The proper functioning of CA may slow progression of AD-associated NFT pathology, and this relationship may be influenced by amount and distribution of phospho-tau (pTau) produced, age, sex, and genetic risk.ObjectiveThe goal of this study was to determine if CA size and number are associated with hippocampal location and local pTau severity while accounting for variations in age, sex, and genetic risk.MethodsPostmortem brain hippocampal tissue sections from 40 AD and 38 unaffected donors were immunohistochemically stained with AT8 (pTau) and counter stained with periodic acid Schiff (PAS). Stained sections of the CA1 and CA3 regions of the hippocampus were analyzed. The percent area occupied (%AO) of CA, pTau, and NFT was calculated. Pairwise comparisons and regression modeling were used to analyze the influence of age, pTau %AO, and genetic risk on %AO by CA in each region, separately in donors with AD and unaffected donors.ResultsCA %AO was significantly higher in the CA3 region compared to CA1 in both groups. A significant negative correlation of CA %AO with both pTau %AO and neurofibrillary tangle %AO in the CA3 region of AD brain donors was found. Regression analysis in the CA3 region revealed a significant negative association between CA with both pTau and age.ConclusionWe found an increase of CA in the CA3 region, compared to CA1 region, in AD and unaffected donors. This may suggest that the CA3 region is a hub for waste removal. Additionally, the negative correlation between %AO by CA and NFT in the CA3 region of the hippocampus in donors with AD suggests CA could play a role in AD pathologic progression by influencing tau clearance.

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“…Another important factor may be sleep disorders. In this sense, a high number of wasteosomes have also been described in the brains of patients with obstructive sleep apnea in a quantitative study performed by Xu et al ( 71 ). In that study, a large number of these structures were detected in almost all the specimens examined.…”

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confidence: 85%

Wasteosomes ( corpora amylacea ) as a hallmark of chronic glymphatic insufficiency

Riba

Valle

Molina‐Porcel

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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In different organs and tissues, the lymphatic system serves as a drainage system for interstitial fluid and is useful for removing substances that would otherwise accumulate in the interstitium. In the brain, which lacks lymphatic circulation, the drainage and cleaning function is performed by the glymphatic system, called so for its dependence on glial cells and its similar function to that of the lymphatic system. In the present article, we define glymphatic insufficiency as the inability of the glymphatic system to properly perform the brain cleaning function. Furthermore, we propose that corpora amylacea or wasteosomes, which are protective structures that act as waste containers and accumulate waste products, are, in fact, a manifestation of chronic glymphatic insufficiency. Assuming this premise, we provide an explanation that coherently links the formation, distribution, structure, and function of these bodies in the human brain. Moreover, we open up new perspectives in the study of the glymphatic system since wasteosomes can provide information about which variables have the greatest impact on the glymphatic system and which diseases occur with chronic glymphatic insufficiency. For example, based on the presence of wasteosomes, it seems that aging, sleep disorders, and cerebrovascular pathologies have the highest impact on the glymphatic system, whereas neurodegenerative diseases have a more limited impact. Furthermore, as glymphatic insufficiency is a risk factor for neurodegenerative diseases, information provided by wasteosomes could help to define the strategies and actions that can prevent glymphatic disruptions, thus limiting the risk of developing neurodegenerative diseases.

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Quantitative analysis of size and regional distribution of corpora amylacea in the hippocampal formation of obstructive sleep apnoea patients

Cited by 8 publications

References 38 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

Corpora amylacea negatively correlate with hippocampal tau pathology in Alzheimer’s disease

Wasteosomes ( corpora amylacea ) as a hallmark of chronic glymphatic insufficiency

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