C9orf72 promoter hypermethylation is neuroprotective: Neuroimaging and neuropathologic evidence

Neurology
Corey T McMillanEdward B Lee

Abstract

To use in vivo neuroimaging and postmortem neuropathologic analysis in C9orf72 repeat expansion patients to investigate the hypothesis that C9orf72 promoter hypermethylation is neuroprotective and regionally selective. Twenty patients with a C9orf72 repeat expansion participating in a high-resolution MRI scan and a clinical examination and a subset of patients (n = 11) were followed longitudinally with these measures. Gray matter (GM) density was related to C9orf72 promoter hypermethylation using permutation-based testing. Regional neuronal loss was measured in an independent autopsy series (n = 35) of C9orf72 repeat expansion patients. GM analysis revealed that hippocampus, frontal cortex, and thalamus are associated with hypermethylation and thus appear to be relatively protected from mutant C9orf72. Neuropathologic analysis demonstrated an association between reduced neuronal loss and hypermethylation in hippocampus and frontal cortex. Longitudinal neuroimaging revealed that hypermethylation is associated with reduced longitudinal decline in GM regions protected by hypermethylation and longitudinal neuropsychological assessment demonstrated that longitudinal decline in verbal recall is protected by hypermethylation. These cr...Continue Reading

Citations

Nov 29, 2015·Neurologic Clinics·Roger E Kelley, Ramy El-Khoury
Apr 10, 2016·Brain Research·Aaron D Gitler, Hitomi Tsuiji
Sep 22, 2015·Frontiers in Aging Neuroscience·Alberto BenussiBarbara Borroni
May 4, 2016·Neuroscience and Biobehavioral Reviews·Song ChiJin-Tai Yu
May 7, 2016·Nature Reviews. Neuroscience·Aaron R HaeuslerJeffrey D Rothstein
Jun 11, 2016·Acta Neuropathologica·Veronique V BelzilLeonard Petrucelli
Mar 27, 2016·Journal of Neurochemistry·Tiffany W Todd, Leonard Petrucelli
Jan 4, 2017·Molecular Psychiatry·R Delgado-Morales, M Esteller
Jan 29, 2017·Cold Spring Harbor Perspectives in Medicine·Tania F Gendron, Leonard Petrucelli
Jan 29, 2017·Cold Spring Harbor Perspectives in Medicine·Ilse GijselinckChristine Van Broeckhoven
May 5, 2017·Disease Models & Mechanisms·Elaine Y LiuEdward B Lee
Nov 5, 2019·Nucleic Acids Research·Christopher P CaliEdward B Lee
Nov 14, 2019·The EMBO Journal·Bart SwinnenLudo Van Den Bosch
Jun 14, 2017·Molecular Neurodegeneration·Rustam EsanovZane Zeier
Nov 2, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jie Jiang, John Ravits
Oct 18, 2019·Neurology·Massimo Filippi, Corey T McMillan
Sep 21, 2019·Neurology·Carrie CaswellLauren M Massimo
Sep 3, 2020·Acta Neuropathologica·Elke BraemsLudo Van Den Bosch
Sep 8, 2017·Acta Neuropathologica Communications·Ahmed YousefJohn Q Trojanowski
Mar 16, 2018·Brain Imaging and Behavior·Lauren MassimoCorey T McMillan
Mar 26, 2019·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Ashley CrookDominic B Rowe
Aug 19, 2018·Nature Reviews. Neurology·Rubika Balendra, Adrian M Isaacs
Feb 27, 2018·PeerJ·Shalini IyerVasanta Subramanian
Nov 18, 2018·Nature Reviews. Neurology·Murray Grossman
Apr 4, 2019·Frontiers in Neurology·Rangariroyashe Hannah ChipikaPeter Bede
Aug 18, 2020·Trends in Immunology·Magdalini Polymenidou
Sep 6, 2020·Neurobiology of Disease·Suvi HäkkinenSuzee E Lee
May 25, 2021·Frontiers in Cellular Neuroscience·Julie SmeyersMorwena Latouche
Aug 13, 2021·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Antonia RattiVincenzo Silani

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.