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Neurobiol Aging. 2016 Nov;47:201-209. doi: 10.1016/j.neurobiolaging.2016.07.030. Epub 2016 Aug 8.

Widespread white matter and conduction defects in PSEN1-related spastic paraparesis.

Author information

1
University of Hawaii, John A. Burns School of Medicine, Honolulu, HI, USA.
2
Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
3
Department of Neurology, Keck School of Medicine of USC Center for the Health Professionals, Los Angeles, CA, USA.
4
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
5
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Mary S. Easton Center for Alzheimer's Disease Research, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
6
Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Neurology, David Geffen School of Medicine, #3506C Gonda Neuroscience and Genetics Research Center, UCLA, Los Angeles, CA, USA.
7
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Mary S. Easton Center for Alzheimer's Disease Research, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Departments of Neurology, Radiology, Medical and Molecular Genetics, Indiana University School of Medicine, Indiana Alzheimer's Disease Center, Indianapolis, IN, USA.
8
Department of Neurology, Keck School of Medicine of USC Center for the Health Professionals, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Mary S. Easton Center for Alzheimer's Disease Research, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: john.ringman@med.usc.edu.

Abstract

The mechanisms underlying presenilin 1 (PSEN1) mutation-associated spastic paraparesis (SP) are not clear. We compared diffusion and volumetric magnetic resonance measures between 3 persons with SP associated with the A431E mutation and 7 symptomatic persons with PSEN1 mutations without SP matched for symptom duration. We performed amyloid imaging and central motor and somatosensory conduction studies in 1 subject with SP. We found decreases in fractional anisotropy and increases in mean diffusivity in widespread white-matter areas including the corpus callosum, occipital, parietal, and frontal lobes in PSEN1 mutation carriers with SP. Volumetric measures were not different, and amyloid imaging showed low signal in sensorimotor cortex and other areas in a single subject with SP. Electrophysiological studies demonstrated both slowed motor and sensory conduction in the lower extremities in this same subject. Our results suggest that SP in carriers of the A431E PSEN1 mutation is a manifestation of widespread white-matter abnormalities not confined to the corticospinal tract that is at most indirectly related to the mutation's effect on amyloid precursor protein processing and amyloid deposition.

KEYWORDS:

Diffusion tensor imaging; Electrophysiology; PSEN1; White matter; spastic paraparesis

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have no conflict of interest to disclose.

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