Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by memory loss and severe cognitive decline. The etiology of the disease has not been explored, although a significant body of evidence suggests that neuronal dysfunction is caused by hyperphosphorylation and intracellular accumulation of the Tau protein, extracellular accumulation of the amyloid β-peptide (Aβ), and the associated chronic activation of glial cells. Clearance of toxic Aβ, apoptotic cells and debris from the brain together with induction of neuronal repair mechanisms may all take place partially throughout the progression of AD, but therapeutic approaches based on knowledge of these processes have been unsuccessfully developed. Here, we address the question of whether autoimmune mechanisms can be boosted to safely facilitate the above-mentioned clearance and neuronal repair in the AD brain. We have previously demonstrated that depending on genetic background, autoimmunity targeted to Aβ is already induced in elderly individuals and in patients with AD. We have shown in a mouse model of AD that given a preexisting proinflammatory milieu in the brain, immune cells can enter the brain tissue and participate in clearance of Aβ. Furthermore, the decline in cognitive functions and neurogenesis throughout the progression of AD may also be affected by autoimmune mechanisms operating in the periphery and in the brain. In light of the so-far unsuccessful anti-inflammatory approaches to treating AD, we suggest that boosting - rather than suppressing - the endogenous immune mechanisms induced in AD may enhance repair pathways in the brain, provided that this approach can be safely applied.
- Alzheimer's disease
- Amyloid β-peptide