Clonally expanded CD8 T cells in spinal fluid of Alzheimer’s patients suggest an adaptive immune response to pathogens

Using immunohistochemistry on post-mortem brains, a group from Stanford found that Alzheimer’s brains had significantly more CD8+ T cells in the brain, especially near the hippocampus and Aβ plaques. This prompted the researches to take a closer look.

In a new study published in Nature, a group led by neuroscientist Tony Wyss-Coray at Stanford found a surprising number of CD8+ T cells that suggesting that the adaptive immune response in these Alzheimer’s (AD) patients had been activated against specific pathogens.  Although they have not been able to confirm the target(s) of these T cells, preliminary evidence suggests that at least one set of T cell receptors was targeted at Epstein Barr virus.

CD8+ T cells in controls vs Alzheimer’s patients.

Mass cytometry also revealed that AD patients have increase CD8+T effector memory CD45RA+ (TEMRA) cells in their blood. These cells had increased T cell receptor (TCR) signaling. They also showed that the presence of these CD8+TEMRA cells was associated with lower cognition.

AD patients, and patients with mild cognitive impairment (MCI), had clonally expanded CD8+TEMRA cells in their cerebrospinal fluid more frequently compared to controls. In one case, a single clone made up 44% of all CD8+ TCRs. Additionally, most clones had increased expression of cytotoxic and inflammatory functions, many of which have be previously associated with AD. Interestingly, two AD individuals and one MCI individual had clonally expanded CD8+TEMRA cells which had shared specificity to EBV.

The authors note that these observations do not confirm a role of pathogens in the development of AD, however they do raise questions as to why highly specific and clonally expanded T cells are being recruited in and around AD brains, especially as the debate over the role of pathogens in AD continues into 2020.

Read the full paper: Gate 2020