Ringman John M, Casado Maria, Van Berlo Victoria, Pa Judy, Joseph-Mathurin Nelly, Fagan Anne M, Benzinger Tammie, Bateman Randall J, Morris John C
Department of Neurology, Keck School of Medicine of the University of Southern California, 1540 Alcazar Street, Suite 209F, Los Angeles, CA, 90033, USA; Mary S. Easton Center for Alzheimer's Disease Research, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Room C-224, Los Angeles, CA 90095-1769, USA.
Mary S. Easton Center for Alzheimer's Disease Research, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Room C-224, Los Angeles, CA 90095-1769, USA.
Neurosci Lett. 2017 Sep 14;657:11-15. doi: 10.1016/j.neulet.2017.07.046. Epub 2017 Jul 29.
We describe clinical and biomarker findings in an index patient with the onset of Alzheimer's disease (AD) symptoms at age 57 and a family history consistent with an autosomal dominant pattern of inheritance. She had the atypical early features of visual agnosia and prosopagnosia followed by hoarding behavior and Parkinsonism. Structural MRI revealed global atrophy that was most severe in the lateral temporal lobes and insular cortex bilaterally. CSF biomarker assessment showed Aβ42, p-tau, and total tau levels consistent with AD. Genetic assessment revealed a novel mutation in the PSEN1 gene (S230N) in the index patient and her affected brother which was absent in her two clinically unaffected and AD-biomarker negative sisters. The serine residue at codon 230 in PSEN1 is highly conserved across species and in PSEN2, providing strong evidence for its pathogenicity in this family.
我们描述了一名索引患者的临床和生物标志物研究结果，该患者57岁时出现阿尔茨海默病（AD）症状，家族史符合常染色体显性遗传模式。她具有视觉失认和面孔失认等非典型早期特征，随后出现囤积行为和帕金森症。结构磁共振成像显示全脑萎缩，双侧颞叶外侧和岛叶皮质萎缩最为严重。脑脊液生物标志物评估显示Aβ42、磷酸化tau蛋白和总tau蛋白水平与AD相符。基因评估发现索引患者及其患病兄弟的PSEN1基因存在一个新突变（S230N），而她的两个临床未受影响且AD生物标志物呈阴性的姐妹则没有该突变。PSEN1基因第230位密码子的丝氨酸残基在物种间和PSEN2中高度保守，有力证明了其在该家族中的致病性。
