Th17 Cells Play a Role in Alzheimer’s Disease

Neuroinflammation mediated by Th17 cells in the brain has been linked to the neurodegeneration characterized in Alzheimer’s disease.¹

Alzheimer’s disease (AD) is the number one cause of dementia, which is classified as a loss of cognitive functioning due to neurodegeneration.^♯ AD is most common in people over the age of 60, and over 5 million Americans are estimated to have the disease.^♯ With the “baby boomer” generation entering this age group, increased understanding of AD is even more important in order to treat an aging population.

Healthy Brain vs. Alzheimer's Disease Brain

Many changes occur in the brains of people with Alzheimer’s disease. For an interactive tour of these changes, click here. Changes to the hippocampus and cortex are responsible for increased memory loss and decreased cognitive function. An overall shrinking of the brain and increase in the size of the ventricles occurs. These changes increase over time and are irreversible.

Currently, the most well understood cause of Alzheimer’s is due to a buildup of amyloid-β (Aβ) plaques.² These plaques develop when a protein called APP is cleaved by enzymes to create Aβ. The hippocampus and neocortex of the brain are most vulnerable to the plaques, which are responsible for behavioral and functional deficits of AD.² However, new research has targeted neuroinflammation as an important component in AD progression.³ Some experiments have shown that inflammatory mediators stimulate APP breakdown to further contribute to the disease.³


In a recent experiment conducted by Ju Zhang et al., the effects of Th17 immune cells in the brain of AD-model rats were studied.¹ Th17 cells are a type of differentiated helper T leukocyte. Helper T cells are characterized by the presence of the coreceptor CD4 and are important for adaptive immune function. Th17 cells specifically are responsible for inflammation through the release of cytokine “danger signals,” such as IL-17 and IL-22 and for autoimmune response.¹

Based on the knowledge that Th17 cells are involved in neuroinflammation and in Alzheimer’s brains, Zhang et al. hypothesized that Th17 cells are directly responsible for neuronal cell death through the interaction of transmembrane proteins Fas and FasL.¹ Fas and FasL are well-known receptors and ligands, respectively, which are involved in a pathway for apoptosis (programmed cell death). Fas exists on neurons, and FasL is located on the surface of Th17 cells.¹ The binding of these proteins is able to occur in AD brains, because a faulty blood-brain barrier (BBB) allows T cells to cross it, leading to elevated levels of Th17 cells in brain parenchyma.⁴ This does not occur in healthy brains, and, as we can see, has negative effects.

Sprague-Dawley rat

To test the hypothesis, it was necessary to induce rats to develop brain changes that would imitate AD. In this experiment, 4-month-old Sprague-Dawley rats were used.¹ Aβ was injected into the hippocampi to induce neurodegenerative changes that have been shown to imitate both pathological and behavioral characteristics of AD.⁵ Rats were studied 7 or 14 days following the injection. APP expression was upregulated and neuron loss occurred and the changes showed greater progression in AD-like changes from 7 to 14 days.¹

The study also demonstrated the effect of AD on the BBB of the rats. The BBB was shown to be impaired through the presence of immunoreactive cells for RORγ in the hippocampus of AD-model rats compared with control and saline-injected rats.¹ RORγ is a transcriptional factor specific to Th17 cells, and RORγ-positive cells indicate that the BBB in AD brains is faulty and allows Th17 to leak into the hippocampus.