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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Wander, CM; Tsujimoto, THM; Ervin, JF; Wang, C; Maranto, SM; Bhat, V; Dallmeier, JD; Wang, S-HJ; Lin, F-C; Scott, WK; Holtzman, DM; Cohen, TJ

Published Date

  • August 8, 2022

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 110 -

PubMed ID

  • 35941704

Pubmed Central ID

  • PMC9361643

Electronic International Standard Serial Number (EISSN)

  • 2051-5960

Digital Object Identifier (DOI)

  • 10.1186/s40478-022-01409-5

Language

  • eng

Conference Location

  • England