The Impact of Aging on Brain Pituitary Adenylate Cyclase Activating Polypeptide, Pathology and Cognition in Mice and Rhesus Macaques
Permenter, Michele R.
Vogt, Julie A.
Engle, James R.
Dugger, Brittany N.
Beach, Thomas G.
Barnes, Carol A.
AffiliationUniv Arizona, Div Neural Syst Memory & Aging
Univ Arizona, Dept Psychol
Univ Arizona, Dept Neurol
Univ Arizona, Dept Neurosci
MetadataShow full item record
PublisherFRONTIERS MEDIA SA
CitationThe Impact of Aging on Brain Pituitary Adenylate Cyclase Activating Polypeptide, Pathology and Cognition in Mice and Rhesus Macaques 2017, 9 Frontiers in Aging Neuroscience
JournalFrontiers in Aging Neuroscience
Rights© 2017 Han, Nielsen, Song, Yin, Permenter, Vogt, Engle, Dugger, Beach, Barnes and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractPituitary adenylate cyclase activating polypeptide (PACAP) is associated with Alzheimer's disease (AD), but its age-related effects are unknown. We chose the rhesus macaque due to its closeness to human anatomy and physiology. We examined four variables: aging, cognitive performance, amyloid plaques and PACAP. Delayed nonmatching-to-sample recognition memory scores declined with age and correlated with PACAP levels in the striatum, parietal and temporal lobes. Because amyloid plaques were the only AD pathology in the old rhesus macaque, we further studied human amyloid precursor protein (hAPP) transgenic mice. Aging was associated with decreased performance in the Morris Water Maze (MWM). In wild type (WT) C57BL/ 6 mice, the performance was decreased at age 24-26 month whereas in hAPP transgenic mice, it was decreased as early as 9-12 month. Neuritic plaques in adult hAPP mice clustered in hippocampus and adjacent cortical regions, but did not propagate further into the frontal cortex. Cerebral PACAP protein levels were reduced in hAPP mice compared to age-matched WT mice, but the genetic predisposition dominated cognitive decline. Taken together, these data suggest an association among PACAP levels, aging, cognitive function and amyloid load in nonhuman primates, with both similarities and differences from human AD brains. Our results suggest caution in choosing animal models and in extrapolating data to human AD studies.
NoteOpen Access Journal
VersionFinal published version
SponsorsAlzheimer Association New Investigator Research Grant [AA-NIRG-14-322078]; Arizona Alzheimer Disease Consortium Pilot Grant [NIH/NIA-P30 AG19610]; Arizona Alzheimer Disease Consortium Pilot Grant (State of Arizona/Arizona Department of Health Services (ADHS)); McKnight Brain Research Foundation; Barrow Neurological Foundation Project; National Science Foundation of China ; NIH [R01 AG003376, P51 RR000169]