Amyloid-β plaques may be reduced in advanced stages of cerebral amyloid angiopathy in the elderly.

淀粉样蛋白-β 斑块在老年人脑淀粉样血管病的晚期可能减少。

  • 影响因子:2.09
  • DOI:10.1111/neup.12662
  • 作者列表:"Okamoto K","Amari M","Fukuda T","Suzuki K","Takatama M
  • 发表时间:2020-06-17

:We examined 29 cases in which cerebral amyloid angiopathy (CAA) was detected among routine aged autopsies. Most cases with severe CAA had many amyloid-β (Aβ) plaques in the occipital cortex. Nonetheless, two cases had few Aβ plaques with many small vessels and capillaries with CAA. In the two cases, severe CAA was widely distributed, except in the frontal lobes. Aβ deposits in capillaries often showed the characteristic pattern of dysphoric amyloid angiopathy. A few naked plaques were present. Although Aβ plaques were sparse near small vessels with CAA, there were many Aβ plaques distant from small vessels with CAA. Some of the remaining plaques had a moth-eaten appearance. Based on Aβ-positive star-like appearance and results of double immunohistochemistry for glial fibrillary acidic protein and Aβ1-42 , some astrocytes appeared to contain Aβ. Ionized calcium-binding adapter molecule 1 (Iba1)-positive microglia were scattered within the neuropil, with some present around small vessels with CAA. Iba1-positive microglia also seemed to phagocytose Aβ in several senile plaques by double immunostaining. Neurons and neurites identified with a monoclonal antibody against phosphorylated tau (clone AT8) were occasionally detected in sparse plaque areas, with AT8-identified dot-like structures present around capillaries with CAA. Accumulation of T lymphocytes was detected around vessels in the subarachnoid space in one case. The morphological changes detected in our two cases were similar to those of morphological markers of plaque clearance after Aβ immunotherapy. Nonetheless, our cases did not receive Aβ immunotherapy, but similar pathologies were observed. Overall, advanced CAA cases, including our two cases, may be examples of plaque clearance without Aβ immunotherapy. Further studies are needed to resolve the mechanism of Aβ plaque clearance using these cases.


: 我们检查了 29 例常规老年尸检中检出脑淀粉样血管病 (CAA) 的病例。大多数严重 CAA 的病例在枕叶皮质有许多淀粉样蛋白-β (a β) 斑块。尽管如此,2 例有少量 a β 斑块,有多条小血管和毛细血管伴 CAA。2 例中重度 CAA 分布广泛,额叶除外。毛细血管内 a β 沉积常表现为烦躁不安的淀粉样血管病变的特征性模式。有一些裸露的斑块。虽然 a β 斑块在 CAA 小血管附近稀疏,但在 CAA 小血管附近有许多 a β 斑块。剩余的一些斑块有虫蛀的外观。基于 a β 阳性的星形细胞样外观和胶质纤维酸性蛋白和 a β 1-42 的双重免疫组化结果,一些星形胶质细胞似乎含有 a β。离子钙结合适配器分子 1 (Iba1) 阳性小胶质细胞散在 neuropil 内,一些存在于 CAA 小血管周围。通过双重免疫染色,Iba1-positive 小胶质细胞似乎也吞噬了几种老年斑中的 a β。偶尔在稀疏斑块区域检测到用磷酸化 tau (克隆 AT8) 单克隆抗体鉴定的神经元和神经突,CAA 毛细血管周围存在 AT8-identified 点状结构。1 例检测到蛛网膜下腔血管周围 T 淋巴细胞聚集。我们两例中检测到的形态学变化与 a β 免疫治疗后斑块清除的形态学标志物相似。尽管如此,我们的病例没有接受 a β 免疫治疗,但观察到类似的病理。总体而言,晚期 CAA 病例,包括我们的两例,可能是无 a β 免疫治疗的斑块清除的例子。使用这些病例需要进一步的研究来解决 a β 斑块清除的机制。



来源期刊:Physical therapy
作者列表:["Thilarajah S","Bower KJ","Hao PY","Tan D","Williams G","Larik A","Wai BC","Koh G","Clark RA"]

METHODS:BACKGROUND:People with stroke are not meeting recommended levels of physical activity. The modifiable factors associated with post-stroke physical activity levels need to be identified to develop targeted interventions. OBJECTIVE:The objective of this study was to investigate the factors at discharge from inpatient rehabilitation that are associated with physical activity levels at 3 months following discharge. DESIGN:This was a prospective cohort study. METHODS:Sixty-four people with stroke completed baseline assessments at discharge from inpatient rehabilitation and 55 completed the follow-up 3 months later. The candidate factors (i.e. gait speed, balance, strength, cognition, mood and motivation) were measured at discharge. The primary outcome measure at follow-up was walking related activity (measured by wrist-worn accelerometer). Secondary outcome measures were physical activity participation (Activity Card Sort) and intensity of physical activity (International Physical Activity Questionnaire - Short 7 days). Adjusted separate multivariable linear regression models or proportional odds regression models were used to evaluate the associations between candidate factors and physical activity. RESULTS:Gait speed and balance were associated with all aspects of physical activity. Higher level of intrinsic motivation was also associated with higher physical activity participation. Anxiety demonstrated a significant non-linear relationship with physical activity participation. LIMITATIONS:Inclusion of fatigue and individual muscle strength could have provided further insights into associations with steps per day. CONCLUSION:The results demonstrated that better physical function at discharge from inpatient rehabilitation was associated with future increased levels of physical activity. Additionally, higher levels of motivation impacted on increased physical activity participation. The influence of anxiety on physical activity participation requires further exploration. Mixed-method study designs can be utilized to further understand the factors associated with post-stroke physical activity.

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作者列表:["Cheng, Xiao","Yang, Ying-Lin","Li, Wei-Han","Liu, Man","Zhang, Shan-Shan","Wang, Yue-Hua","Du, Guan-Hua"]

METHODS:Cerebral ischemia-reperfusion (I/R) is characterized by initial transient cerebral ischemia followed by reperfusion. Various pathophysiological processes are involved in brain injury and functional recovery during cerebral I/R. There are few studies on dynamic metabolic process after cerebral I/R. The present study was to observe dynamic alteration of brain injury, functional recovery, and metabolites after cerebral I/R in rats and discover potential metabolic markers. The cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 90 min, following reperfusion in rats. The results of cerebral infarction area, cerebral edema, and behavior test showed that there were dynamic changes in brain injury and functional recovery at different periods after cerebral I/R. Further analysis showed that the brain injury was severe on the first day of cerebral I/R, and there was a significant functional recovery from the 7th day of cerebral I/R, followed by an aggravation trend of brain injury from the days 7 to 28. Furthermore, Matrix-assisted laser desorption ionization mass spectrometry imaging analysis showed that the expression of ATP, glucose, and citric acid on 7th day was the highest during cerebral I/R, which indicated that energy metabolism and oxidative phosphorylation played important roles during cerebral I/R. In addition, the untargeted metabolomic results showed that the level of isocitric acid, the ratio of oxyglutaric acid/glutamic acid, and the level of pyruvic acid associated with the TCA cycle were also the highest on the 7th day during cerebral I/R, which indicated that the transient spontaneous recovery of ischemic brain on the 7th day after ischemia-reperfusion might be related to oxidative phosphorylation and energy metabolism in the brain in this period. In conclusion, the results suggest that some small molecule metabolites participate in the brain injury and functional recovery during cerebral I/R, which is of great significance to the development of therapeutic drugs and diagnostic markers.

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作者列表:["Wang, Xiaodong","Shi, Cunxian","Pan, Hongxia","Meng, Xiaowen","Ji, Fuhai"]

METHODS:The aims of this study were to study the effects of miR-2 on cerebral ischemia–reperfusion rats and to explore its further mechanism. Rats were assigned into sham, model, miR-22 control and miR-22 groups. Observation of neurological behaviors at 24 h after operation found that neurological functions were severely damaged in the model and miR-22 control groups and these damages were improved by miR-22. RT-PCR indicated that miR-22 mRNA level in the brain tissue was significantly decreased in the model and miR-22 control groups, but increased in the miR-22 group. TTC staining showed increased percentage of cerebral infarction volume in the model and miR-22 control groups and this increase was reduced by miR-22. Immunohistochemistry showed increased densities of CD34^+ and VEGF^+ microvessels in the cortex in the model and miR-22 control groups, which were further increased in the miR-22 group. ELISA showed increased serum VEGF and Ang-1 levels in the model and miR-22 control groups, which were also further increased in the miR-22 group. Western blot analysis showed increased phosphorylation level of PI3K and Akt in brain tissue in the model and miR-22 control groups, which were further increased in the miR-22 group. Administration of LY294002, a specific PI3K pathway inhibitor, significantly reversed all the effects of miR-22 on rats in the model group. miR-22 exerts its neuroprotective and angiogenic functions via the PI3K/Akt signaling pathway, at least partly, in rats under cerebral ischemia–reperfusion.

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