Key result
Lower brain PACAP levels in Alzheimer disease correlate with higher amyloid burden.
Why the study?
There is growing evidence that PACAP is associated with AD pathology in animal models, but human studies are needed.
Case-Control (n=48)
PACAP levels are significantly reduced in the brains of patients with Alzheimer disease and correlate with disease severity, suggesting a potential role in its pathogenesis.
Reduced PACAP associates with advanced Alzheimer pathology; hypothesis-generating and should not yet change practice or guide therapy.
OBJECTIVES: There is growing evidence that pituitary adenylate cyclase-activating polypeptide (PACAP) is associated with Alzheimer disease (AD) pathology in animal models, but human studies are needed. METHODS: We studied the brains of patients with pathologically confirmed late-onset AD and age-matched cognitively normal (CN) subjects to investigate the expression of PACAP messenger RNA (34 AD and 14 CN) and protein (12 AD and 11 CN) in a case-control study. RESULTS: We report that PACAP levels are reduced in multiple brain regions, including the entorhinal cortex, the middle temporal gyrus, the superior frontal gyrus, and the primary visual cortex. This reduction is correlated with higher amyloid burden (CERAD plaque density) in the entorhinal cortex and superior frontal gyrus but not in the primary visual cortex, a region spared in most cases of AD. PACAP expression is lower in advanced Braak stages (V and VI) than in moderate stages (III and IV). Increased PACAP levels are associated with decreased scores on the Dementia Rating Scale, a global cognitive measure. Finally, CSF levels paralleled brain levels in AD but not in Parkinson dementia or frontotemporal dementia brains. CONCLUSIONS: The close relationship between PACAP reduction and the severity of AD pathology suggests that downregulation of PACAP may contribute to AD pathogenesis.
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Han et al. (2014) conducted a case-control in Alzheimer disease (n=48). Alzheimer disease vs. Cognitively normal subjects was evaluated on PACAP messenger RNA and protein expression. PACAP levels are reduced in multiple brain regions in patients with Alzheimer disease compared to cognitively normal subjects, and this reduction correlates with higher amyloid burden.
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