<p>Approved and effective therapies for Alzheimer's disease (AD) are extremely limited given the disease prevalence. Most of the currently approved treatments offer symptom management but do not alter progression. However, the complexity of AD and its many pathological processes present several possible novel intervention points to slow progression. G protein-coupled receptors (GPCRs) can modify major biological functions and over one third of all FDA approved drugs target GPCRs, however they are underrepresented in the Alzheimer’s disease-modifying therapy pipeline. To address the deficiency of this target class for AD, GPCR targets were evaluated for their associations with 48 identified traits of interest related to AD in the Genome Wide Association Study (GWAS) Catalog. We identified 22 GPCRs with at least two linkages to AD traits as potential future targets for therapies. Of the 22 GPCR identified, only three are targets of agents in clinical trials as of Jan 1, 2025. We further analyzed the 22 identified and categorized them into four groups of receptors: adhesion G protein-coupled receptors, adrenoreceptors, metabotropic glutamate receptors, and receptors which did not have other family members with associations. Here we review each of these GPCRs for their potential as targets for AD. The 19 GPCRs with associations but not yet in clinical trials present possibilities to develop therapies that may go beyond symptom management and towards modifying the progression of AD.</p> Graphical Abstract <p></p>