Differential DNA Methylation of the Genes for Amyloid Precursor Protein, Tau, and Neurofilaments in Human Traumatic Brain Injury.
J Neurotrauma
; 38(12): 1679-1688, 2021 06 15.
Article
en En
| MEDLINE
| ID: mdl-33191850
ABSTRACT
Traumatic brain injury (TBI) is an established risk factor for neurodegenerative disorders and dementias. Epigenetic modifications, such as DNA methylation, may alter the expression of genes without altering the DNA sequence in response to environmental factors. We hypothesized that DNA methylation changes may occur in the injured human brain and be implicated in the neurodegenerative aftermath of TBI. The DNA methylation status of genes related to neurodegeneration; for example, amyloid beta precursor protein (APP), microtubule associated protein tau (MAPT), neurofilament heavy (NEFH), neurofilament medium (NEFM), and neurofilament light (NEFL), was analyzed in fresh, surgically resected human brain tissue from 17 severe TBI patients and compared with brain biopsy samples from 19 patients with idiopathic normal pressure hydrocephalus (iNPH). We also performed an epigenome-wide association study (EWAS) comparing TBI patients with iNPH controls. Thirty-eight CpG sites in the APP, MAPT, NEFH, and NEFL genes were differentially methylated by TBI. Among the top 20 differentially methylated CpG sites, 11 were in the APP gene. In addition, the EWAS evaluating 828,888 CpG sites revealed 308 differentially methylated CpG sites in genes related to cellular/anatomical structure development, cell differentiation, and anatomical morphogenesis. These preliminary findings provide the first evidence of an altered DNA methylome in the injured human brain, and may have implications for the neurodegenerative disorders associated with TBI.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Filamentos Intermedios
/
Precursor de Proteína beta-Amiloide
/
Proteínas tau
/
Metilación de ADN
/
Lesiones Traumáticas del Encéfalo
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Neurotrauma
Asunto de la revista:
NEUROLOGIA
/
TRAUMATOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Suecia