The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease
The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease
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DOI：
10.1016/j.biopsych.2006.06.017
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发表时间：
2006-12-15
影响因子：
10.6
通讯作者：
Lieberman, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Marx, Christine E.;Trost, William T.;Lieberman, Jeffrey A.
背景：目前研究神经类固醇（NS）治疗阿尔茨海默病（AD）的数据很少。 AD 患者血清和血浆中的 NS 四氢孕酮可能降低，但尚不清楚脑中四氢孕酮是否也降低。由于许多 NS 在啮齿动物模型中表现出神经保护作用并影响认知表现，因此这些分子可能与神经退行性疾病的病理生理学相关。因此，我们研究了 AD 中的前额皮质 (PFC) NS 水平。方法：通过气相色谱质谱法，然后进行高效液相色谱法，测定 14 名 AD 男性受试者和 15 名认知完好的男性对照受试者死后 PFC 中的神经类固醇水平（别孕酮、孕烯醇酮、脱氢表雄酮 [DHEA]） 结果：与认知完好的对照受试者相比，AD 受试者的四氢孕酮显着降低（中位水平分别 = 2.50 ng/g vs 5.59 ng/g；p = .02）。四氢孕酮水平与神经病理疾病阶段 (Braak) 呈负相关，r = -.49，p = .007。 AD 受试者的中位 DHEA 水平升高 (p = .01)。结论：AD 受试者的 PFC 四氢孕酮水平显着降低，这一发现可能与神经病理学疾病阶段的严重程度相关。神经类固醇可能可作为 AD 的候选生物标志物。
Background: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD.Methods: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography mass spectrometry preceded by high-performance liquid chromatography purification.Results: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs, 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01).Conclusions: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.