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Alzheimer's & dementia : the journal of the Alzheimer's Association
Published

Basic Science and Pathogenesis

Authors

Regina T Vontell, Ayled Barreda, Kaj Blennow, Henrik Zetterberg, Juan Pablo de Rivero Vaccari, Helen M Bramlett, W Dalton Dietrich, Robert W Keane, David A Davis, Tatjana Rundek, Xiaoyan Sun

Abstract

Alzheimers Dement. 2024 Dec;20 Suppl 1:e089239. doi: 10.1002/alz.089239.

ABSTRACT

BACKGROUND: Neurogranin (Ng) is considered a biomarker for synaptic dysfunction in Alzheimer's disease (AD). In contrast, the inflammasome complex has been shown to exacerbate AD pathology.

METHOD: We investigated the protein expression, morphological differences of Ng and correlated Ng to hyperphosphorylated tau in the postmortem brains of 17 AD cases and 17 age and sex-matched controls. In addition, we correlated the Ng expression with two different epitopes of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC).

RESULT: We show a reduction of Ng immunopositive neurons and morphological differences in AD compared to controls. Ng immunostaining was negatively correlated with neurofibrillary tangles, humanized anti-ASC (IC100) positive neurons and anti- ASC positive microglia, in AD.

CONCLUSION: The finding of a negative correlation between Ng and ASC speck protein expression in postmortem brains of AD suggests that the activation of inflammasome/ASC speck pathway may play an important role in synaptic degeneration in AD.

PMID:39751051 | DOI:10.1002/alz.089239

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg