Chronic inflammation contributes to the onset and progression of all of the common age-related conditions. Researchers can examine a population of patients with a specific age-related disease and note specific differences in the immune system that contribute to inflammation. Because one is selecting for patients with greater inflammation by selecting those with the condition means that this sort of study may or may not represent a useful advance in knowledge. The need for better, more sophisticated approaches to reduce the chronic inflammation of old age is well understood. Some of these studies could reveal targets for the development of novel anti-inflammatory treatments, many will not.
The real challenge inherent to efforts to reduce late-life chronic inflammation is that, so far, it appears that the systems of regulation involved in maladaptive chronic inflammation are exactly the same as those needed for normal, transient inflammation. Changing the operation of the immune system to suppress unwanted inflammation also suppresses necessary inflammation, weakening the immune response to pathogens and potentially cancerous cells. The best path forward is to remove the age-related damage and dysfunction that provokes the immune system into inflammatory behavior, but comprehensively identifying and addressing all of those mechanisms that is a somewhat more distant prospect than the development of further ways to alter immune function.
Phenotypic alterations in peripheral blood B Lymphocytes of patients with Alzheimer's Disease
The immune system plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Microglia, the primary phagocytic cells in the brain, are responsible for the clearance of the amyloid-β (Aβ) and tau proteins. A significant number of AD-associated risk genes identified through genome-wide association studies (GWAS) are linked to the immune system. However, the phenotype and functional aspects of humoral immunity in AD remain incompletely understood. Our previous studies reported a panel of autoantibodies that are involved in the pathogenesis of AD. Other studies have also identified various autoantibodies in the circulation and cerebrospinal fluid of AD patients. In the AD brain, many brain-reactive autoantibodies are associated with Aβ deposition, supporting an autoimmune hypothesis in AD. Nevertheless, the mechanisms underlying the dysregulated autoantibody profile in AD have yet to be fully addressed.
B lymphocytes, a key component of the adaptive immune system, not only function as antigen-presenting cells to activate T cells and regulate inflammatory responses but also play a pivotal role in humoral immunity by secreting autoantibodies. We evaluated the immunophenotype of peripheral B lymphocytes in 27 AD patients confirmed by PET-Amyloid scan and 32 cognitively normal controls. We show that the phenotype of B lymphocytes is altered in AD patients. AD patients exhibit a decrease in both the numbers and proportions of switched memory (SwM) B cells and double-negative (DN) B cells. Additionally, B cells that produce proinflammatory cytokines including GM-CSF, IFN-γ, and TNF-α are increased, while those that produce the anti-inflammatory cytokine IL-10 are decreased in AD patients after in vitro stimulation. These alterations in B cell populations were linked to cognitive functions and biomarkers, including Aβ42/40 and pTau181, in AD patients.
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