CD2AP in Alzheimer's disease: Key mechanisms and therapeutic potential

Alzheimer's disease affects millions worldwide as one of the most devastating neurodegenerative conditions, characterized by two distinct pathological features: amyloid plaques (composed of clustered β-amyloid peptides) and neurofibrillary tangles (made of hyperphosphorylated Tau protein). These hallmark changes trigger a cascade of events, including progressive synaptic dysfunction, inflammation, and the breakdown of the protective blood–brain barrier. Recent breakthrough research through genome-wide association studies has identified CD2-associated protein (CD2AP) as a significant risk factor in developing Alzheimer's disease, with this crucial adaptor protein emerging as a key player in several disease mechanisms due to its fundamental role in cellular transport and cytoskeletal architecture. Growing evidence reveals that CD2AP influences multiple aspects of Alzheimer's disease pathogenesis, from β-amyloid metabolism and deposition to Tau-mediated neurotoxicity, synaptic integrity, blood–brain barrier function, and microglial activation states. Understanding CD2AP's physiological and pathological roles in the nervous system, particularly its cell type-specific functions, is crucial for developing effective therapeutic strategies that target CD2AP levels for Alzheimer's prevention and treatment, requiring a comprehensive understanding of CD2AP biology in neuronal cells.