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

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 C...

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Bibliographic Details
Published in:	Acta neuropathologica communications Vol. 10; no. 1; p. 110
Main Authors:	Wander, Connor M, Tsujimoto, Tamy Harumy Moraes, Ervin, John F, Wang, Chanung, Maranto, Spencer M, Bhat, Vanya, Dallmeier, Julian D, Wang, Shih-Hsiu Jerry, Lin, Feng-Chang, Scott, William K, Holtzman, David M, Cohen, Todd J
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 08-08-2022 BioMed Central BMC
Subjects:	Advertising executives Alzheimer Disease - metabolism Alzheimer's disease Amyloid beta-Peptides - metabolism Analysis Animal cognition Animals Antibodies Apolipoproteins Apolipoproteins E - metabolism Brain Brain - pathology Cognition Generalized linear models Genetic engineering Humans Mice Neurodegeneration Pathology Phosphorylation tau Proteins - metabolism
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2051-5960 2051-5960
DOI:	10.1186/s40478-022-01409-5