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Neurosci Lett. 2017 Sep 14;657:11-15. doi: 10.1016/j.neulet.2017.07.046. Epub 2017 Jul 29.

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

Author information

1
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. Electronic address: John.ringman@med.usc.edu.
2
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.
3
Semel Institute for Neuroscience and Human Behavior, 695 Charles Young Drive South, Los Angeles, CA 90095, USA.
4
Department of Neurology, Keck School of Medicine of the University of Southern California, 1540 Alcazar Street, Suite 209F, Los Angeles, CA, 90033, USA; Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, 2025 Zonal Ave, Los Angeles, CA 90033, USA.
5
Mallinckrodt Institute of Radiology, Washington University in St. Louis, 510 S. Kingshighway Blvd. #1610, St. Louis, MO, 63110, USA.
6
Department of Neurology, Washington University in St. Louis, 660 S. Euclid Ave, St. Louis, MO, 63110, USA.

Abstract

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-tau181, 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.

KEYWORDS:

Hoarding; Novel; PSEN1; Parkinsonism; Prosopagnosia; S230N; Visual agnosia

PMID:
28764909
PMCID:
PMC5731478
DOI:
10.1016/j.neulet.2017.07.046
[Indexed for MEDLINE]
Free PMC Article

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