The Influence of Relationships Within Behavioral Weight Management Interventions: An Overview.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder primarily affecting the elderly and is characterized by a gradual decline in cognitive and brain function (). Amyloid-β (Aβ) is established as a central component of the widely accepted amyloid cascade hypothesis of AD and a principal constituent of the hallmark plaques associated with neuropathology (). Mechanistically, Aβ is thought to contribute to disease progression by driving synaptic dysfunction, processes that disrupt neuronal communication within the brain (). Aβ is generated from the sequential cleavage of amyloid precursor protein (APP) by β-secretases and γ-secretases (, ). This cleavage produces monomeric soluble Aβ peptides of varying lengths, with Aβ40 and Aβ42 being the most common isoforms (). Once generated, Aβ monomers are amyloidogenic and spontaneously aggregate into oligomeric assemblies, including low-molecular-weight dimers and trimers, as well as larger protofibrils and insoluble fibrils (). These fibrillar structures ultimately accumulate into large insoluble amyloid plaques, which are notably resistant to proteolytic degradation, detergents, heat, and can persist in tissue over time (). Aβ was initially considered a pathogenic byproduct of APP metabolism with no specific cellular function; however, Aβ is now confirmed to be produced under normal physiological conditions and plays important roles in various cellular processes. Examples include maintenance of blood-brain barrier integrity, promotion of injury repair, regulation of synaptic function, and, most recently, antimicrobial defense (). One line of evidence supporting a physiological role for Aβ in innate immunity comes from experimental and structural analyses. Collectively, these studies indicate that Aβ shares key structural and functional features with antimicrobial peptides (AMPs), including the human cathelicidin LL-37 and several bacteriocins that kill or neutralize microbial pathogens (). Like canonical AMPs, Aβ is an amphipathic, low-molecular-weight peptide lacking cysteine residues and possessing a hydrophobic C-terminus, a conserved heparin-binding motif, and an inherent propensity to oligomerize (). Importantly, oligomerization and aggregation are recognized as physiological attributes of many AMPs that enhance antimicrobial efficacy (). Together, these experimental and structural parallels positioned Aβ as a host defense peptide and provided a strong rationale for further experiments directly assessing its antimicrobial activity. This review explores the evolving view of Aβ as an immune effector molecule with antimicrobial properties.