Presenilin 1 (PSEN1) is a critical component of the γ-secretase complex, a multisubunit protease responsible for the intramembrane cleavage of various type I transmembrane proteins, including amyloid precursor protein (APP). Cleavage of APP by γ-secretase generates amyloid-β (Aβ) peptides, particularly Aβ42. which aggregates into plaques in Alzheimer’s disease (AD). Mutations in the PSEN1 gene are the most common cause of early-onset familial AD, highlighting its central role in Aβ pathology. PSEN1 antibodies are essential tools for studying its expression, localization, and function in both physiological and pathological contexts. These antibodies target specific epitopes of the PSEN1 protein, enabling detection in techniques like Western blotting, immunohistochemistry, and immunoprecipitation. Researchers use them to investigate PSEN1 processing (e.g., cleavage into N- and C-terminal fragments), interactions with γ-secretase subunits, and alterations in AD models or patient tissues. Some antibodies distinguish between full-length PSEN1 and its proteolytic fragments, aiding in studies of its maturation and activity. Additionally, PSEN1 antibodies are employed to validate knockout or knockdown models and assess mutant PSEN1 effects on Aβ production. Their applications extend to exploring PSEN1’s non-proteolytic roles in calcium homeostasis, autophagy, and Wnt signaling. As dysregulated PSEN1 contributes broadly to neurodegeneration, these antibodies remain pivotal in advancing AD research and therapeutic development targeting γ-secretase activity.