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Box A: Diversity of GPCR ligands Neurotransmitters norepinephrine adenosine histamine serotonin dopamine cannabinoids opiates acetylcholine GABA glutamate Peptide hormones endothelin glucagon angiotensin II GSH, FSH, CRH GnRH, ACTH Tastants, oderants, light Learning Objectives 1

Despite the rarity of each individual condition, rare diseases collectively affect over 400 million people worldwide 1 approximately eight times the global number of cancer patients 2

From these metrics, participants were stratified into four clinical groups: neuropathological AD diagnosis with dementia (dementia, 25 participants), neuropathological AD diagnosis without dementia (resilient, 25 participants), no AD or other neurological disease diagnosis with dementia (frail, 26 participants), and a control group with no AD or other neurological disease diagnosis and negligible cognitive decline at time of death (control, 26 participants)