A novel PSEN1 (S230N) mutation causing early -onset Alzheimer's Disease associated with prosopagnosia, hoarding, and Parkinsonism

NEUROSCIENCE LETTERS

卷:657

Article

Ringman, John M.^1,2  Casado, Maria²  Van Berlo, Victoria³  Pa, Judy^1,4  Joseph-Mathurin, Nelly⁵  Fagan, Anne M.⁶  Benzinger, Tammie⁵  Bateman, Randall J.⁶  Morris, John C.⁶ 

[1] Univ Southern Calif, Keck Sch Med, Dept Neurol, 1540 Alcazar St,Suite 209F, Los Angeles, CA USA

[2] UCLA, David Geffen Sch Med, Mary S Easton Ctr Alzheimers Dis Res, 710 Westwood Plaza,Room C-224, Los Angeles, CA 90095 USA

[3] Semel Inst Neurosci & Human Behav, 695 Charles Young Dr South, Los Angeles, CA 90095 USA

[4] Univ Southern Calif, Keck Sch Med, Mark & Mary Stevens Neuroimaging & Informat Inst, 2025 Zonal Ave, Los Angeles, CA 90033 USA

[5] Washington Univ, Mallinckrodt Inst Radiol, 510 S Kingshighway Blvd 1610, St Louis, MO 63110 USA

[6] Washington Univ, Dept Neurol, 660 S Euclid Ave, St Louis, MO 63110 USA

关键词: PSEN1;    Novel;    S230N;    Prosopagnosia;    Hoarding;    Parkinsonism;    Visual agnosia;   

DOI  :  10.1016/j.neulet.2017.07.046

来源: Elsevier

【 摘 要 】

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 A1342, p-taui81, 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. (C) 2017 Elsevier B.V. All rights reserved.

【 授权许可】

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