TitleWidespread white matter and conduction defects in PSEN1-related spastic paraparesis.
Publication TypeJournal Article
Year of Publication2016
AuthorsSoosman SK, Joseph-Mathurin N, Braskie MN, Bordelon YM, Wharton D, Casado M, Coppola G, McCallum H, Nuwer M, Coutin-Churchman P, Apostolova LG, Benzinger T, Ringman JM
JournalNeurobiol Aging
Date Published2016 11
KeywordsAmyloid beta-Protein Precursor, Amyloidogenic Proteins, Anisotropy, Diffusion Tensor Imaging, Electrophysiological Phenomena, Female, Genetic Association Studies, Humans, Male, Middle Aged, Motor Cortex, Mutation, Neural Conduction, Paraparesis, Spastic, Presenilin-1, Somatosensory Cortex, White Matter

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.

Alternate JournalNeurobiol. Aging
PubMed ID27614114
PubMed Central IDPMC5075491
Grant ListUL1 RR033176 / RR / NCRR NIH HHS / United States
U01 AG051218 / AG / NIA NIH HHS / United States
P50 AG005142 / AG / NIA NIH HHS / United States
M01 RR000865 / RR / NCRR NIH HHS / United States
R01 EB009352 / EB / NIBIB NIH HHS / United States
P50 AG016570 / AG / NIA NIH HHS / United States
K08 AG022228 / AG / NIA NIH HHS / United States
UF1 AG032438 / AG / NIA NIH HHS / United States
UL1 TR000448 / TR / NCATS NIH HHS / United States
T35 AG026736 / AG / NIA NIH HHS / United States
U19 AG032438 / AG / NIA NIH HHS / United States