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Elevation of CD69+ monocyte/macrophages in patients with Alzheimer's disease

L Kusdra1, H Rempel, K Yaffe

  • 1Department of Laboratory Medicine, Veteran's Affairs Medical Center, San Francisco, California 94121, USA.

Immunobiology
|July 6, 2000
PubMed

Insights

Alzheimer's disease patients show increased CD69 activation markers on monocytes. While these cells may reflect brain pathology, their conditioned media, surprisingly, showed reduced neurotoxicity, suggesting they aren't directly causing neural cell damage.

Area of Science:

  • Neuroimmunology
  • Cellular Biology
  • Neurology

Background:

  • Previous research indicated elevated CD14+/CD69+ monocyte subsets in AIDS dementia patients, with toxic effects on neural cultures.
  • This study investigates if a similar monocyte subset elevation occurs in Alzheimer's disease (AD) and correlates with neurotoxicity.

Purpose of the Study:

  • To determine the percentage of CD69+ monocytes in Alzheimer's disease patients compared to controls.
  • To assess the neurotoxic potential of monocyte-conditioned media from AD patients.
  • To explore the relationship between monocyte activation markers and neurotoxicity in AD.

Main Methods:

  • Flow cytometry was used to analyze CD69 and HLA-DR expression on monocytes from AD patients and age-matched controls.
  • Side scatter (SSC) was measured as an indicator of cellular granularity.
  • Neurotoxicity assays were performed on neural cell aggregates using conditioned media from monocyte cultures.
  • Electrophoretic mobility shift assays (EMSA) were used to detect NF-kappaB activation.

Main Results:

  • AD patients exhibited a statistically significant higher percentage of CD69+ monocytes compared to controls (p = 0.006).
  • Elevated side scatter (cellular granularity) was observed in monocytes from AD patients (p = 0.02).
  • Three out of five tested AD patient monocyte supernatants induced apoptosis in neural cell cultures, and these also triggered NF-kappaB translocation.
  • Unexpectedly, in vitro neurotoxicity was associated with supernatants from monocyte cultures showing a lower percentage of CD14+/CD69+ cells.

Conclusions:

  • Alzheimer's disease patients have an increased proportion of CD69+ monocytes in peripheral blood.
  • This monocyte subset elevation may reflect central nervous system pathological processes in AD.
  • The CD14+/CD69+ monocyte subset itself may not be directly responsible for the observed in vitro neurotoxicity in AD.

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