From the Barrow Neurological Institute (P.H., L.C.B., J.Y., Z.T., J.S.), St. Joseph Hospital and Medical Center, Dignity Health Organization, Phoenix; Translational Genomics Research Institute (W.L.), Phoenix, AZ; Department of Neurosurgery (Z.T.), The First Hospital of Kunming Medical University, Kunming, China; Civin Laboratory for Neuropathology (T.G.B.), Banner Sun Health Research Institute, Sun City; Department of Neurology (R.J.C.), Mayo Clinic Arizona, Scottsdale; and Banner Alzheimer's Institute (E.M.R.), Phoenix, AZ.
Neurology. 2014 May 13;82(19):1724-8. doi: 10.1212/WNL.0000000000000417. Epub 2014 Apr 9.
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.
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.
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.
The close relationship between PACAP reduction and the severity of AD pathology suggests that downregulation of PACAP may contribute to AD pathogenesis.
越来越多的证据表明，垂体腺苷酸环化酶激活肽（PACAP）与动物模型中的阿尔茨海默病（AD）病理有关，但仍需要人类研究。
我们研究了经病理证实的晚发性 AD 患者和年龄匹配的认知正常（CN）受试者的大脑，以在病例对照研究中调查 PACAP 信使 RNA（34 例 AD 和 14 例 CN）和蛋白（12 例 AD 和 11 例 CN）的表达。
我们报告称，PACAP 水平在多个脑区降低，包括内嗅皮层、颞中回、额上回和初级视觉皮层。这种减少与内嗅皮层和额上回的淀粉样蛋白负荷（CERAD 斑块密度）较高相关，但与初级视觉皮层无关，AD 病例中该区域通常未受累。在高级 Braak 阶段（V 和 VI），PACAP 表达低于中度阶段（III 和 IV）。PACAP 水平升高与痴呆评定量表（一种全面认知测量）的评分降低相关。最后，CSF 水平与 AD 患者的脑水平平行，但与帕金森痴呆或额颞叶痴呆患者的脑水平不同。
PACAP 减少与 AD 病理严重程度的密切关系表明，PACAP 的下调可能有助于 AD 的发病机制。
