T cells could be key for early Alzheimer’s detection

T cells could be key for early Alzheimer's detection
Mechanism of action of a cytotoxic T cell like the TEMRA cell subpopulation found in Alzheimer’s brain patients

For a long time Alzheimer disease has been studied mostly as a neuronal disease. However, recently the role of the immune system is getting more attention and its involvement more clear. Recent research 1 has shown that a subpopulation of T cells could be key to early Alzheimer’s detection.

How were these T cells discovered?

Firstly, from blood samples of healthy volunteers and people with Alzheimer’s or mild cognitive impairment (MCI), which is its precursor, they isolated immune cells. Then they found a subpopulation of so-called CD8+ T effector memory CD45RA+(TEMRA) cells associated with MCI and Alzheimer’s disease.

What do these TEMRA cells do in Alzheimer’s?

TEMRA cells are part of the adaptive immune system, the one that helps us fight an infection after getting a vaccine, and release inflammatory and cytotoxic (cell-death-promoting) molecules.

In Alzheimer patients, the researchers found a correlation between TEMRA levels and cognitive deterioration. This result could be due to the increased presence of TEMRA cells in the hippocampus (involved in memory) and their high levels of expression of cytotoxic genes, that eventually kill neurons.

In vitro studies also confirmed that the responses of isolated T cells to an antigen was higher in people affected by Alzheimer’s or MCI than in healthy people.

The post-mortem analysis of Alzheimer’s brain samples also showed an increased presence of TEMRA in close contact to areas of amyloid-ß deposition. TEMRA cells can produce neuronal damage not only by cytokine release but also by direct neurite loss.

Moreover, analysis of cerebrospinal fluid (CSF) of Alzheimer’s and MCI patients showed an increase in the presence of a clonal derived population of TEMRA cells.

T EMRA cells could be key to early Alzheimer’s detection

The authors showed that using a machine learning algorithm, measurements of TEMRA cell populations (together with other immune information) could distinguish healthy people from those suffering from Alzheimer’s or MCI with about 80% accuracy. Since the amount of TEMRA cells do not change with ageing, it might hold potential as an early biomarker for the disease. Together with other techniques like indicators of neuronal damage or cognitive tests, it might be the key to early detection of Alzheimer’s.

References

  1. Davud gate et al. (2020) Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease Nature doi: 10.1038/s41586-019-1895-7

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