Kalaria R N
Department of Neurology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Ann N Y Acad Sci. 1997 Sep 26;826:263-71. doi: 10.1111/j.1749-6632.1997.tb48478.x.
Current evidence is not inconsistent with the suggestion that cerebrovascular functions decline during normal aging with pronounced effects in both sporadic and familial Alzheimer's disease (AD). The primary causes of these changes remain unknown. It is possible that amyloid beta (A beta) protein is involved in the degeneration of both the larger penetrating vessels as well as the cerebral capillaries that represent the blood-brain barrier (BBB). A beta-induced endothelial changes could also alter muscular tone, resulting not only in increased expression of vascular amyloid precursor protein (APP) and production of A beta, but also in oxidative injury. We used immunochemical methods to examine the status of the perfusing cerebral vessels and the microvascular endothelium in relation to deposition of A beta in AD and non-AD aging control subjects. Double-immunostaining with antibodies to vascular markers revealed marked loss of smooth muscle in larger vessels and absence or attenuation of the endothelium in capillary profiles that still appeared to retain their basement membranes. These vascular changes were predominantly restricted to neocortical regions abundant in A beta deposits. Quantitative studies showed that the microvascular abnormalities were correlated to A beta deposition rather than neurofibrillary tangles or neuronal numbers. Our studies suggest that A beta, irrespective of its origin within vascular myocytes or brain parenchyma, is responsible not only for cerebral amyloid angiopathy, but also for the degeneration of the cerebral microvasculature, which may profoundly affect brain perfusion and BBB functions.
在正常衰老过程中脑血管功能会下降，在散发性和家族性阿尔茨海默病（AD）中均有显著影响。这些变化的主要原因尚不清楚。淀粉样β蛋白（Aβ）可能参与了较大的穿通血管以及代表血脑屏障（BBB）的脑毛细血管的退化。Aβ诱导的内皮细胞变化也可能改变肌肉张力，不仅导致血管淀粉样前体蛋白（APP）表达增加和Aβ产生，还会导致氧化损伤。我们使用免疫化学方法检查灌注脑血管和微血管内皮的状态，以及它们与AD和非AD衰老对照受试者中Aβ沉积的关系。用血管标记物抗体进行双重免疫染色显示，较大血管中的平滑肌明显丧失，毛细血管轮廓中的内皮细胞缺失或减弱，而这些毛细血管似乎仍保留其基底膜。这些血管变化主要局限于富含Aβ沉积物的新皮质区域。定量研究表明，微血管异常与Aβ沉积相关，而不是与神经原纤维缠结或神经元数量相关。我们的研究表明，无论Aβ起源于血管肌细胞还是脑实质，它不仅是脑淀粉样血管病的原因，也是脑微血管退化的原因，这可能会深刻影响脑灌注和血脑屏障功能。
