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Transcriptomic analysis of age-associated periventricular lesions reveals dysregulation of the immune response

ABSTRACT: Transcriptomic analysis of age-associated periventricular lesions reveals dysregulation of the immune response

PROVIDER: PRJNA661058 | ENA |

REPOSITORIES: ENA

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Transcriptomic analysis of age-associated periventricular lesions reveals dysregulation of the immune response

Project description:Age-associated Periventricular white matter lesions (PVL), reflecting white matter injury, are a common feature of the ageing brain. The aim of this study was to evaluate the transcriptomic profile of PVL using microarray analysis, in order to identify which pathways and/or gene expression changes may contribute to the pathogenesis of these lesions.

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Transcriptomic Analysis of Age-Associated Periventricular Lesions Reveals Dysregulation of the Immune Response.

Project description:White matter lesions (WML) are a common feature of the ageing brain associated with cognitive impairment. The gene expression profiles of periventricular lesions (PVL, n = 7) and radiologically-normal-appearing (control) periventricular white matter cases (n = 11) obtained from the Cognitive Function and Ageing Study (CFAS) neuropathology cohort were interrogated using microarray analysis and NanoString to identify novel mechanisms potentially underlying their formation. Histological characterisation of control white matter cases identified a subgroup (n = 4) which contained high levels of MHC-II immunoreactive microglia, and were classified as "pre-lesional." Microarray analysis identified 2256 significantly differentially-expressed genes (p ? 0.05, FC ? 1.2) in PVL compared to non-lesional control white matter (1378 upregulated and 878 downregulated); 2649 significantly differentially-expressed genes in "pre-lesional" cases compared to PVL (1390 upregulated and 1259 downregulated); and 2398 significantly differentially-expressed genes in "pre-lesional" versus non-lesional control cases (1527 upregulated and 871 downregulated). Whilst histological evaluation of a single marker (MHC-II) implicates immune-activated microglia in lesion pathology, transcriptomic analysis indicates significant downregulation of a number of activated microglial markers and suggests established PVL are part of a continuous spectrum of white matter injury. The gene expression profile of "pre-lesional" periventricular white matter suggests upregulation of several signalling pathways may be a neuroprotective response to prevent the pathogenesis of PVL.

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