Extravascular CD3+ T Cells in Brains of Alzheimer Disease Patients Correlate with Tau but Not with Amyloid Pathology: An Immunohistochemical Study

Neurodegener Dis. 2018;18(1):49-56. doi: 10.1159/000486200. Epub 2018 Feb 7.

Abstract

Background: Strong genetic and epidemiological evidence points to a crucial role of the immune system in the development of Alzheimer disease (AD). CD3+ T lymphocytes have been described in brains of postmortem AD patients and in transgenic models of AD-like cerebral amyloidosis and tau pathology. However, the occurrence of T cells in AD brains is still controversial; furthermore, the relationship between T cells and hallmarks of AD pathology (amyloid plaques and neurofibrillary tangles) remains to be established.

Objectives: We have studied the occurrence of T cells in postmortem hippocampi and mid frontal gyrus (MFG) samples of AD patients (Braak stage V-VI) and nondemented control subjects and correlated it with amyloid and tau pathology burden.

Methods: Confocal microscopy and bright-field immunohistochemistry were used to identify brain-associated T cells. Extravascular CD3+ T cells were quantified and compared to nondemented controls. In addition, numbers of extravascular CD3+ T cells were correlated with amyloid (6E10 staining) and tau pathology (AT8 staining) in the same sections.

Results: Several CD3+, extravascular T cells were observed in the brains of AD patients, mostly of the CD8+ subtype. AD hippocampi harbored significantly increased numbers of extravascular CD3+ T cells compared to nondemented controls. CD3+ T cells significantly correlated with tau pathology but not with amyloid plaques in AD samples.

Conclusions: Our data support the notion of T-cell occurrence in AD brains and suggest that, in advanced stages of AD, T-cell extravasation is driven by tau-related neurodegenerative changes rather than by cerebral amyloidosis. T cells could be crucial for driving the amyloid-independent phase of the AD pathology.

Keywords: 6E10; AT8; Alzheimer disease; Amyloid; CD3; Hippocampus; Mid frontal gyrus; T cells; Tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Brain / immunology*
  • Brain / metabolism
  • Brain / pathology
  • CD3 Complex / immunology*
  • CD3 Complex / metabolism
  • Female
  • Humans
  • Male
  • Plaque, Amyloid / immunology*
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • CD3 Complex