Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States of America.
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, United States of America.
PLoS One. 2019 Aug 12;14(8):e0220968. doi: 10.1371/journal.pone.0220968. eCollection 2019.
Alzheimer's disease and related disorders (ADRD) may manifest cognitive and non-cognitive phenotypes including motor impairment, suggesting a shared underlying biology. We tested the hypothesis that five cortical proteins identified from a gene network that drives AD and cognitive phenotypes are also related to motor function in the same individuals. We examined 1208 brains of older adults with motor and cognitive assessments prior to death. Cortical proteins were quantified with SRM proteomics and we collected indices of AD and other related pathologies. A higher level of IGFBP5 was associated with poorer motor function proximate to death but AK4, HSPB2, ITPK1 and PLXNB1 were unrelated to motor function. The association of IGFBP5 with motor function was unrelated to the presence of indices of brain pathologies. In contrast, the addition of a term for cognition attenuated the association of IGFBP5 with motor function by about 90% and they were no longer related. These data lend support for the idea that unidentified cortical proteins like IGFBP5, which may not manifest a known pathologic footprint, may contribute to motor and cognitive function in older adults.
阿尔茨海默病及相关疾病（ADRD）可能表现出认知和非认知表型，包括运动障碍，提示存在共同的潜在生物学机制。我们检验了一个假设，即从驱动 AD 和认知表型的基因网络中鉴定出的五种皮质蛋白也与同一人群的运动功能有关。我们检查了 1208 个老年人的大脑，这些大脑在死亡前进行了运动和认知评估。皮质蛋白用 SRM 蛋白质组学进行了定量分析，我们还收集了 AD 和其他相关病理的指标。IGFBP5 水平较高与接近死亡时的运动功能较差相关，但 AK4、HSPB2、ITPK1 和 PLXNB1 与运动功能无关。IGFBP5 与运动功能的关联与脑病理指标的存在无关。相比之下，加入认知指标会使 IGFBP5 与运动功能的关联减弱约 90%，它们不再相关。这些数据支持这样一种观点，即像 IGFBP5 这样未被识别的皮质蛋白可能与运动和认知功能有关，而它们可能没有表现出已知的病理特征。
