Michalski Bernadeta, Corrada Maria M, Kawas Claudia H, Fahnestock Margaret
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Department of Epidemiology, University of California, Irvine, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Neurobiol Aging. 2015 Dec;36(12):3130-3139. doi: 10.1016/j.neurobiolaging.2015.08.022. Epub 2015 Aug 29.
Factors associated with maintaining good cognition into old age are unclear. Decreased brain-derived neurotrophic factor (BDNF) contributes to memory loss in Alzheimer's disease (AD), and soluble assemblies of amyloid-beta (Aβ) and tau contribute to neurodegeneration. However, it is unknown whether AD-type neuropathology, soluble Aβ and tau, or levels of BDNF and its receptor tropomyosin-related kinase B (TrkB) correlate with dementia in the oldest-old. We examined these targets in postmortem Brodmann's areas 7 and 9 (BA7 and BA9) in 4 groups of subjects >90 years old: (1) no dementia/no AD pathology, (2) no dementia/AD pathology, (3) dementia/no AD pathology, (4) dementia/AD pathology. In BA7, BDNF messenger RNA correlated with Mini-Mental State Examination scores and was decreased in demented versus nondemented subjects, regardless of pathology. Soluble Aβ42 was increased in both groups with AD pathology, demented or not, compared to no dementia/no AD pathology subjects. Groups did not differ in TrkB isoform levels or in levels of total soluble tau, individual tau isoforms, threonine-181 tau phosphorylation, or ratio of phosphorylated 3R-4R isoforms. In BA9, soluble Aβ42 correlated with Mini-Mental State Examination scores and with BDNF messenger RNA expression. Thus, soluble Aβ42 and BDNF, but not TrkB or soluble tau, correlate with dementia in the oldest-old.
与步入老年后仍保持良好认知相关的因素尚不清楚。脑源性神经营养因子（BDNF）水平降低会导致阿尔茨海默病（AD）患者出现记忆丧失，而β-淀粉样蛋白（Aβ）和tau蛋白的可溶性聚集体会导致神经退行性变。然而，尚不清楚AD型神经病理学、可溶性Aβ和tau蛋白，或BDNF及其受体原肌球蛋白相关激酶B（TrkB）的水平是否与高龄老人的痴呆症相关。我们在4组年龄超过90岁的受试者的尸检布罗德曼7区和9区（BA7和BA9）中检测了这些指标：（1）无痴呆症/无AD病理学改变；（2）无痴呆症/有AD病理学改变；（3）有痴呆症/无AD病理学改变；（4）有痴呆症/有AD病理学改变。在BA7中，BDNF信使核糖核酸与简易精神状态检查表评分相关，且在痴呆受试者与非痴呆受试者中均降低，与病理学改变无关。与无痴呆症/无AD病理学改变的受试者相比，有AD病理学改变的两组受试者（无论是否患有痴呆症）的可溶性Aβ42均升高。各组在TrkB亚型水平、总可溶性tau蛋白水平、单个tau蛋白亚型、苏氨酸-181 tau蛋白磷酸化水平或磷酸化3R-4R亚型比例方面无差异。在BA9中，可溶性Aβ42与简易精神状态检查表评分以及BDNF信使核糖核酸表达相关。因此，可溶性Aβ42和BDNF，而非TrkB或可溶性tau蛋白，与高龄老人的痴呆症相关。
