Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, and Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou, 510080, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China.
Mol Neurobiol. 2018 Feb;55(2):1703-1713. doi: 10.1007/s12035-017-0446-1. Epub 2017 Feb 16.
Alzheimer's disease (AD) is characterized by progressive neuronal degeneration and pathological accumulation of amyloid plaques in the brain. It has been proposed that the prion-like spreading of amyloid beta (Aβ) protein could contribute to the progression of the disease. Olfactory bulb (OB) is one of the earliest brain regions affected in AD and olfaction is easily impaired prior to cognitive symptoms. However, it remains unclear whether Aβ accumulation in the OB would spread along olfactory projections to other connected brain regions and trigger further neurodegeneration. In the present study, we experimentally injected recombinant human Aβ1-42 (monomers and oligomers, respectively) into the mouse OB and tracked the spreading of Aβ to connected brain regions over 3 days. The results showed that both Aβ monomers and oligomers were rapidly and readily transferred from the injection site to interconnected brain regions in a neural connection manner and triggered neuronal apoptosis in the affected brain regions. Oligomeric Aβ1-42 spread more efficiently and induced more neuronal apoptosis in the affected brain regions compared to monomeric Aβ1-42. Therefore, the study provides evidence that Aβ peptides can transfer via neural connections and the pattern of Aβ peptide spreading provides understanding to manage AD.
阿尔茨海默病（AD）的特征是神经元进行性退化和大脑中淀粉样斑块的病理性积累。有人提出，淀粉样β（Aβ）蛋白的类朊病毒样扩散可能有助于疾病的进展。嗅球（OB）是 AD 最早受影响的大脑区域之一，嗅觉在认知症状出现之前很容易受损。然而，目前尚不清楚 OB 中的 Aβ 积累是否会沿着嗅觉投射纤维传播到其他连接的大脑区域并引发进一步的神经退行性变。在本研究中，我们将重组人 Aβ1-42（单体和寡聚体）分别注入小鼠 OB，并在 3 天内跟踪 Aβ 向连接的脑区的扩散。结果表明，Aβ 单体和寡聚体都以神经连接的方式从注射部位迅速且容易地转移到相互连接的脑区，并在受影响的脑区引发神经元凋亡。与 Aβ1-42 单体相比，寡聚 Aβ1-42 更有效地扩散，并在受影响的脑区诱导更多的神经元凋亡。因此，该研究提供了证据表明 Aβ 肽可以通过神经连接转移，并且 Aβ 肽的扩散模式为 AD 的管理提供了理解。
