Basic Science and Pathogenesis

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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Brain* / metabolism
  • Brain* / pathology
  • CARD Signaling Adaptor Proteins / metabolism
  • Female
  • Humans
  • Inflammasomes / metabolism
  • Male
  • Microglia / metabolism
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Neurogranin* / metabolism
  • Neurons / metabolism
  • Neurons / pathology
  • tau Proteins / metabolism

Substances

  • Neurogranin
  • tau Proteins
  • CARD Signaling Adaptor Proteins
  • Inflammasomes
  • PYCARD protein, human