阿尔茨海默症的特点是沉积的老年斑块和逐步严重的痴呆症状。然而，目前这种斑块的沉积与神经系统发生故障的分子机制尚且未知。
利用转基因小鼠模型联同多光子成像技术，Kuchibhotla等人利用基因编码的钙离子敏感蛋白YC 3.6，在体内研究了一些神经突起和神经刺体内的神经元钙。相关论文发表在7月31日的《神经元》（Neuron）杂志上。
定量的成像结果显示，随着大脑皮层斑块的出现，在APP小鼠神经突起中钙含量超过20％；相比之下，在野生型、PS1突变小鼠或年轻的APP小鼠中的钙含量少于5％。钙含量高与斑块有关。接下来的研究结果表明，相应的棘-树突触中钙区域在减少，同时神经元形态发生变形，这部分是由钙调磷酸酶引起的变化。
总之，新的研究数据表明，老年斑块损害了体内神经元的钙稳态，从而导致神经元网络结构与功能的破坏。（生物谷Bioon.com）
生物谷推荐原始出处：
Neuron，Vol 59, 214-225, 31 July 2008，Kishore V. Kuchibhotla, Brian J. Bacskai
Aβ Plaques Lead to Aberrant Regulation of Calcium Homeostasis In Vivo Resulting in Structural and Functional Disruption of Neuronal Networks
Kishore V. Kuchibhotla,1,2 Samuel T. Goldman,1 Carli R. Lattarulo,1 Hai-Yan Wu,1 Bradley T. Hyman,1 and Brian J. Bacskai1,
1 Massachusetts General Hospital, Department of Neurology/Alzheimer's Disease Research Laboratory, 114 16th Street, Charlestown, MA 02129, USA
2 Program in Biophysics, Harvard University, Cambridge, MA 02138, USA
Corresponding author
Brian J. Bacskai
Summary
Alzheimer's disease is characterized by the deposition of senile plaques and progressive dementia. The molecular mechanisms that couple plaque deposition to neural system failure, however, are unknown. Using transgenic mouse models of AD together with multiphoton imaging, we measured neuronal calcium in individual neurites and spines in vivo using the genetically encoded calcium indicator Yellow Cameleon 3.6. Quantitative imaging revealed elevated [Ca2+]i (calcium overload) in ～20% of neurites in APP mice with cortical plaques, compared to less than 5% in wild-type mice, PS1 mutant mice, or young APP mice (animals without cortical plaques). Calcium overload depended on the existence and proximity to plaques. The downstream consequences included the loss of spinodendritic calcium compartmentalization (critical for synaptic integration) and a distortion of neuritic morphologies mediated, in part, by the phosphatase calcineurin. Together, these data demonstrate that senile plaques impair neuritic calcium homeostasis in vivo and result in the structural and functional disruption of neuronal networks.
