Alzheimer's Disease: The Past, Present, and Future of a Globally Progressive Disease.

Alzheimer's disease (AD) is a significant 21st-century public health challenge. This article delves into AD's neurodegenerative complexities, highlighting cognitive decline, memory impairment, and societal burdens. Mechanistically, protein misfolding, amyloid-beta (Aß) pathway abnormalities, and genetic/environmental factors are discussed. The pivotal amyloid hypothesis is dissected, focusing on Aß aggregation's role in synaptic dysfunction and neurodegeneration. The review showcases promising therapeutic strategies, including anti-amyloid antibodies and ß/γ-secretase inhibitors targeting Aß production. Notably, the FDA-approved Lecanemab signifies a breakthrough, slowing disease progression. Anti-Tau therapies' emergence is highlighted, addressing late-stage intervention. Tau aggregation blockers and anti-Tau antibodies offer potential against intracellular tau pathology. The review underscores collaborative efforts to uncover AD's secrets and pave the way for memory preservation.

Chimeric antigen receptor T-cell therapy in rheumatology: B-cell depletion 2.0.

PURPOSE OF REVIEW: Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized cancer treatment by harnessing the immune system's power to target malignancies. CD19, a B-cell surface antigen, a key target for CAR-T cell therapy in hematological malignancies, displayed remarkable clinical responses. Recently, there has been a growing interest in exploring the application of CD19 CAR-T cell therapy beyond oncology. The rationale for investigating CD19 CAR-T cells in Rheumatology stems from their ability to selectively target B cells, which play a central pathogenic role through autoantibody-dependent and independent mechanisms. RECENT FINDINGS: Preclinical and five completed clinical studies have shown remarkable efficacy and safety in diseases such as systemic lupus erythematosus, antisynthetase syndrome, and systemic sclerosis. It is thus not surprising that 17 active clinical trials exploring CAR-T cells in Rheumatology are in progress. SUMMARY: Although CAR-T therapy holds great promise in Rheumatology, many challenges loom. Whether this new way to deplete B-cells is superior to conventional antibody-based B-cell depletion in rheumatic diseases will be closely watched in the coming years.