Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Steffan K Soosman  1 , Nelly Joseph-Mathurin  2 , Meredith N Braskie  3 , Yvette M Bordelon  4 , David Wharton  5 , Maria Casado  5 , Giovanni Coppola  6 , Holly McCallum  3 , Marc Nuwer  4 , Pedro Coutin-Churchman  4 , Liana G Apostolova  7 , Tammie Benzinger  2 , John M Ringman  8
Affiliations

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

Steffan K Soosman et al. Neurobiol Aging. 2016 Nov.

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.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflict of interest to disclose.

Figures

Figure 1
Figure 1
A) Voxels in which fractional anisotropy was significantly lower (p < 0.05, FDR corrected) in 3 subjects with PSEN1-related SP relative to 7 without. B) Voxels in which MD was higher and C) radial diffusivity higher in subjects with SP. There were no areas were axial diffusivity differed between groups.
Figure 2
Figure 2
Extensive lobar microhemorrhages seen on susceptibility-weighted MRI in “AJ” a 49 year-old man carrying the A431E PSEN1 mutation with spastic paraparesis. Note the predilection for the parietal and occipital lobes.
Figure 3
Figure 3
PiB images in a subject with SP due to the A431E PSEN1 mutation (“AJ”) and four without SP. Note the overall reduced PiB signal in AJ except for relatively selective deposition in the thalamus.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.
    Joseph-Mathurin N, Feldman RL, Lu R, Shirzadi Z, Toomer C, Saint Clair JR, Ma Y, McKay NS, Strain JF, Kilgore C, Friedrichsen KA, Chen CD, Gordon BA, Chen G, Hornbeck RC, Massoumzadeh P, McCullough AA, Wang Q, Li Y, Wang G, Keefe SJ, Schultz SA, Cruchaga C, Preboske GM, Jack CR Jr, Llibre-Guerra JJ, Allegri RF, Ances BM, Berman SB, Brooks WS, Cash DM, Day GS, Fox NC, Fulham M, Ghetti B, Johnson KA, Jucker M, Klunk WE, la Fougère C, Levin J, Niimi Y, Oh H, Perrin RJ, Reischl G, Ringman JM, Saykin AJ, Schofield PR, Su Y, Supnet-Bell C, Vöglein J, Yakushev I, Brickman AM, Morris JC, McDade E, Xiong C, Bateman RJ, Chhatwal JP, Benzinger TLS; Dominantly Inherited Alzheimer Network. Joseph-Mathurin N, et al. Alzheimers Dement. 2024 Apr;20(4):2680-2697. doi: 10.1002/alz.13729. Epub 2024 Feb 21. Alzheimers Dement. 2024. PMID: 38380882 Free PMC article.
  • Characterization of spastic paraplegia in a family with a novel PSEN1 mutation.
    Ringman JM, Dorrani N, Fernández SG, Signer R, Martinez-Agosto J, Lee H, Douine ED, Qiao Y, Shi Y, D'Orazio L, Pawar S, Robbie L, Kashani AH, Singer M, Byers JT, Magaki S, Guzman S, Sagare A, Zlokovic B, Cederbaum S, Nelson S, Sheikh-Bahaei N, Chui HC, Chávez-Gutiérrez L, Vinters HV. Ringman JM, et al. Brain Commun. 2023 Feb 15;5(2):fcad030. doi: 10.1093/braincomms/fcad030. eCollection 2023. Brain Commun. 2023. PMID: 36895955 Free PMC article.
  • Abnormal retinal capillary blood flow in autosomal dominant Alzheimer's disease.
    Singer MB, Ringman JM, Chu Z, Zhou X, Jiang X, Shahidzadeh A, Wang RK, Kashani AH. Singer MB, et al. Alzheimers Dement (Amst). 2021 Mar 4;13(1):e12162. doi: 10.1002/dad2.12162. eCollection 2021. Alzheimers Dement (Amst). 2021. PMID: 33728371 Free PMC article.
  • The Whole Exome Sequencing Clarifies the Genotype- Phenotype Correlations in Patients with Early-Onset Dementia.
    Xu Y, Liu X, Shen J, Tian W, Fang R, Li B, Ma J, Cao L, Chen S, Li G, Tang H. Xu Y, et al. Aging Dis. 2018 Aug 1;9(4):696-705. doi: 10.14336/AD.2018.0208. eCollection 2018 Aug. Aging Dis. 2018. PMID: 30090657 Free PMC article.
  • Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease.
    Joseph-Mathurin N, Wang G, Kantarci K, Jack CR Jr, McDade E, Hassenstab J, Blazey TM, Gordon BA, Su Y, Chen G, Massoumzadeh P, Hornbeck RC, Allegri RF, Ances BM, Berman SB, Brickman AM, Brooks WS, Cash DM, Chhatwal JP, Chui HC, Correia S, Cruchaga C, Farlow MR, Fox NC, Fulham M, Ghetti B, Graff-Radford NR, Johnson KA, Karch CM, Laske C, Lee AKW, Levin J, Masters CL, Noble JM, O'Connor A, Perrin RJ, Preboske GM, Ringman JM, Rowe CC, Salloway S, Saykin AJ, Schofield PR, Shimada H, Shoji M, Suzuki K, Villemagne VL, Xiong C, Yakushev I, Morris JC, Bateman RJ, Benzinger TLS; Dominantly Inherited Alzheimer Network. Joseph-Mathurin N, et al. Neurology. 2021 Mar 23;96(12):e1632-e1645. doi: 10.1212/WNL.0000000000011542. Epub 2021 Jan 25. Neurology. 2021. PMID: 33495373 Free PMC article.
See all "Cited by" articles

References

    1. Akoudad S, de Groot M, Koudstaal PJ, van der Lugt A, Niessen WJ, Hofman A, et al. Cerebral microbleeds are related to loss of white matter structural integrity. Neurology. 2013 Nov 26;81(22):1930–7. - PubMed
    1. Alzheimer's A. 2015 Alzheimer's disease facts and figures. Alzheimers Dement. 2015 Mar;11(3):332–84. - PubMed
    1. Athan ES, Williamson J, Ciappa A, Santana V, Romas SN, Lee JH, et al. A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families. Jama. 2001;286(18):2257–63. - PubMed
    1. Back SA, Kroenke CD, Sherman LS, Lawrence G, Gong X, Taber EN, et al. White matter lesions defined by diffusion tensor imaging in older adults. Ann Neurol. 2011 Sep;70(3):465–76. - PMC - PubMed
    1. Bozzali M, Falini A, Franceschi M, Cercignani M, Zuffi M, Scotti G, et al. White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging. J Neurol Neurosurg Psychiatry. 2002 Jun;72(6):742–6. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources