Szot P, Leverenz J B, Peskind E R, Kiyasu E, Rohde K, Miller M A, Raskind M A
Northwest Network Mental Illness Research, Education and Clinical Center, Veterans Administration Puget Sound Health Care System, Seattle, WA 98108, USA.
Brain Res Mol Brain Res. 2000 Dec 8;84(1-2):135-40. doi: 10.1016/s0169-328x(00)00168-6.
Despite the loss of locus coeruleus (LC) noradrenergic neurons in Alzheimer's disease (AD), cerebrospinal fluid norepinephrine (NE) levels are normal or increased in AD. This paradox suggests compensatory upregulation of NE synthetic capacity or downregulation of the NE transporter (NET) in the remaining LC neurons. LC tyrosine hydroxylase (TH) mRNA expression in the LC was measured in AD subjects (n=5) and in age and gender comparable non-demented subjects (n=6). When AD subjects were divided into those still ambulatory prior to death (CDR 3/4) and those in a prolonged 'vegetative' state prior to death (CDR 5), differences among groups became apparent at specific levels of the LC. In CDR 3/4 AD subjects there was increased TH mRNA expression per neuron compared to non-demented subjects in the caudal half of the LC. However, expression of NET mRNA in the same subjects was not significantly different at any level of the LC. These preliminary results suggest an upregulation of NE biosynthetic capacity in at least some LC neurons in AD prior to the very late stage of the disease.
尽管在阿尔茨海默病（AD）中蓝斑（LC）去甲肾上腺素能神经元会丧失，但AD患者脑脊液中的去甲肾上腺素（NE）水平正常或升高。这一矛盾现象表明，剩余LC神经元中NE合成能力存在代偿性上调或NE转运体（NET）下调。在AD患者（n = 5）以及年龄和性别匹配的非痴呆患者（n = 6）中测量了LC中酪氨酸羟化酶（TH）mRNA的表达。当将AD患者分为死前仍能行走的患者（临床痴呆评定量表[CDR] 3/4）和死前处于长期“植物人”状态的患者（CDR 5）时，在LC的特定水平上，各组之间的差异变得明显。在CDR 3/4的AD患者中，与非痴呆患者相比，LC尾侧半部每个神经元的TH mRNA表达增加。然而，同一组患者在LC的任何水平上，NET mRNA的表达均无显著差异。这些初步结果表明，在AD疾病的极晚期之前，至少部分LC神经元中NE生物合成能力上调。
