Crook R, Verkkoniemi A, Perez-Tur J, Mehta N, Baker M, Houlden H, Farrer M, Hutton M, Lincoln S, Hardy J, Gwinn K, Somer M, Paetau A, Kalimo H, Ylikoski R, Pöyhönen M, Kucera S, Haltia M
Mayo Clinic Jacksonville, Florida 32084, USA.
Nat Med. 1998 Apr;4(4):452-5. doi: 10.1038/nm0498-452.
We describe a novel variant of Alzheimer's disease (AD) in a Finnish pedigree with 17 affected individuals of both sexes in three generations. The disease is characterized by progressive dementia which is, in most cases, preceded by spastic paraparesis. Neuropathological investigations revealed numerous, distinct, large, round and eosinophilic plaques as well as neurofibrillary tangles and amyloid angiopathy throughout the cerebral cortex. The predominant plaques resembled cotton wool balls and were immunoreactive for Abeta but lacked a congophilic dense core or marked plaque-related neuritic pathology. Molecular genetic analysis revealed that the disease was caused by a deletion of exon 9 (delta9) of the presenilin 1 (PS1) gene from the mRNA: unlike previous examples of the delta9 variant, the deletion was not caused by a splice acceptor site mutation.
我们在一个芬兰家系中描述了一种阿尔茨海默病（AD）的新型变体，该家系三代中有17名男女患者。这种疾病的特征是进行性痴呆，在大多数情况下，在出现痉挛性截瘫之前就会出现。神经病理学研究显示，整个大脑皮层有大量、独特、大的、圆形和嗜酸性斑块，以及神经原纤维缠结和淀粉样血管病。主要的斑块类似棉球，对β淀粉样蛋白具有免疫反应性，但缺乏嗜刚果红的致密核心或明显的与斑块相关的神经炎性病理。分子遗传学分析表明，该疾病是由早老素1（PS1）基因mRNA中外显子9（Δ9）的缺失引起的：与之前的Δ9变体例子不同，这种缺失不是由剪接受体位点突变引起的。
