Theofilas Panos, Dunlop Sara, Heinsen Helmut, Grinberg Lea Tenenholz
Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil.
J Alzheimers Dis. 2015;46(1):17-34. doi: 10.3233/JAD-142682.
Pharmacological interventions in Alzheimer's disease (AD) are likely to be more efficacious if administered early in the course of the disease, foregoing the spread of irreversible changes in the brain. Research findings underline an early vulnerability of the isodendritic core (IC) network to AD neurofibrillary lesions. The IC constitutes a phylogenetically conserved subcortical system including the locus coeruleus in pons, dorsal raphe nucleus, and substantia nigra in the midbrain, and nucleus basalis of Meynert in basal forebrain. Through their ascending projections to the cortex, the IC neurons regulate homeostasis and behavior by synthesizing aminergic and cholinergic neurotransmitters. Here we reviewed the evidence demonstrating that neurons of the IC system show neurofibrillary tangles in the earliest stages of AD, prior to cortical pathology, and how this involvement may explain pre-amnestic symptoms, including depression, agitation, and sleep disturbances in AD patients. In fact, clinical and animal studies show a significant reduction of AD cognitive and behavioral symptoms following replenishment of neurotransmitters associated with the IC network. Therefore, the IC network represents a unique candidate for viable therapeutic intervention and should become a high priority for research in AD.
如果在阿尔茨海默病（AD）病程早期进行药物干预，可能会更有效，从而避免大脑中不可逆变化的扩散。研究结果强调了异树突核心（IC）网络在AD早期易受神经原纤维病变影响。IC构成一个系统发育上保守的皮质下系统，包括脑桥中的蓝斑、中脑中的背侧缝核和黑质，以及基底前脑的Meynert基底核。通过其向皮质的上行投射，IC神经元通过合成胺能和胆碱能神经递质来调节体内平衡和行为。在此，我们回顾了相关证据，这些证据表明IC系统的神经元在AD的最早阶段，即在皮质病变之前就出现了神经原纤维缠结，以及这种受累情况如何解释遗忘前症状，包括AD患者的抑郁、躁动和睡眠障碍。事实上，临床和动物研究表明，补充与IC网络相关的神经递质后，AD的认知和行为症状会显著减轻。因此，IC网络是可行治疗干预的独特候选者，应成为AD研究的高度优先事项。
