The Pituitary Adenylate Cyclase Activating Polypeptide Levels are Associated with Pathological Features of Alzheimer’s Disease (P4.201)

Objective: We investigated the relevance of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) in Alzheimer’s disease (AD). Background: PACAP is a neurotrophin. There is growing evidence of its efficacy in reducing Alzheimer’s pathology in animal models but human studies are lacking. Design/methods: We investigated the expression of PACAP mRNA and protein in the brains of pathologically confirmed late onset AD patients compared with age matched cognitively normal controls (n=33 for mRNA, n=23 for protein). Results: We discovered reduced levels of both in the brain regions susceptible to Alzheimer’s pathology, including the entorhinal cortex (ENT), the middle temporal gyrus (MTG), the superior frontal gyrus (SFG) and the primary visual cortex (PVC), This reduction inversely correlated with amyloid burden (CERAD plaque density) in the ENT, MTG and SFG but not the PVC, a region spared in most cases of AD. PACAP expression is significantly decreased in the advanced Braak Stage (V-VI) in the moderate stage (III-IV). Conclusions: The close inverse relationship between PACAP reduction and AD pathological features suggests that downregulation of PACAP mRNA and protein expression may contribute to AD pathogenesis. Study Supported by: This work is funded by Arizona Alzheimer’s Disease Consortium and Barrow Neurological Foundation. Disclosure: Dr. Shi has nothing to disclose.