Lippa C F, Schmidt M L, Nee L E, Bird T, Nochlin D, Hulette C, Mori H, Lee V M, Trojanowski J Q
Department of Neurology, MCP-Hahnemann University, Philadelphia, PA 19102, USA.
Neurology. 2000 Jan 11;54(1):100-4. doi: 10.1212/wnl.54.1.100.
To assess AMY expression in familial AD (FAD).
The discovery of nonbeta-amyloid (Abeta), plaque-like deposits composed of a 100-kd protein (AMY) in sporadic AD (SAD) brains prompted us to determine whether these plaques (AMY plaques) also occur in AD due to mutations of the presenilin-1 (PS-1), presenilin-2 (PS-2), or the amyloid precursor protein (APP) genes.
We used immunohistochemistry and confocal laser scanning microscopy to probe the brains of 22 patients with FAD (13 with PS-1, 5 with PS-2, and 4 with APP mutations) and 14 patients with SAD.
AMY plaques were present in all SAD and FAD brains, including an FAD/PS-1 brain from an individual with preclinical disease. The morphology of AMY plaques in SAD and FAD brains was indistinguishable, but they differed from Abeta deposits because AMY plaques lacked an immunoreactive core. AMY plaques sometimes colocalized with Abeta(x-42) deposits, but they did not colocalize with Abeta(x-40) plaque cores in either SAD or FAD brains. The percent of cortical area occupied by AMY was greater in FAD than in SAD brains (mean percent area = 9.8% and 5.9%, t = 2.487, p = 0.018). In particular, APP and PS-1 cases had more AMY deposition than PS-2 or SAD cases (12.9%, 10.5%, 6.2% in APP, PS-1, and PS-2 AD).
AMY plaques are consistently present in familial AD due to presenilin-1 (PS-1), PS-2, and amyloid precursor protein mutations, and they can begin to accumulate before the emergence of dementia.
评估淀粉样前体蛋白（AMY）在家族性阿尔茨海默病（FAD）中的表达。
在散发性阿尔茨海默病（SAD）脑内发现了由一种100 kDa蛋白（AMY）组成的非β淀粉样蛋白（Aβ）、斑块样沉积物，这促使我们确定这些斑块（AMY斑块）是否也存在于因早老素-1（PS-1）、早老素-2（PS-2）或淀粉样前体蛋白（APP）基因突变导致的阿尔茨海默病中。
我们使用免疫组织化学和共聚焦激光扫描显微镜检查了22例FAD患者（13例PS-1突变、5例PS-2突变和4例APP突变）以及14例SAD患者的脑。
AMY斑块存在于所有SAD和FAD脑内，包括一名处于临床前期疾病个体的FAD/PS-1脑。SAD和FAD脑内AMY斑块的形态无法区分，但它们与Aβ沉积物不同，因为AMY斑块缺乏免疫反应性核心。AMY斑块有时与Aβ（x-42）沉积物共定位，但在SAD或FAD脑内它们均不与Aβ（x-40）斑块核心共定位。FAD脑内AMY占据的皮质面积百分比高于SAD脑（平均面积百分比分别为9.8%和5.9%，t = 2.487，p = 0.018）。特别是，APP和PS-1病例的AMY沉积比PS-2或SAD病例更多（APP、PS-1和PS-2型阿尔茨海默病分别为12.9%、10.5%、6.2%）。
由于早老素-1（PS-1）、PS-2和淀粉样前体蛋白突变导致的家族性阿尔茨海默病中始终存在AMY斑块，并且它们在痴呆出现之前就可能开始积累。
