G2C4 targeting antisense oligonucleotides potently mitigate TDP-43 dysfunction in human C9orf72 ALS/FTD induced pluripotent stem cell derived neurons
AbstractThe G4C2 repeat expansion in the C9orf72 gene is the most common genetic cause of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Many studies suggest that dipeptide repeat proteins produced from this repeat are toxic, yet, the contribution of repeat RNA toxicity is under investigated and even less is known regarding the pathogenicity of antisense repeat RNA. Recently, two clinical trials targeting G4C2 (sense) repeat RNA via antisense oligonucleotide failed despite a robust decrease in sense-encoded dipeptide repeat proteins demonstrating target engagement. Here, in this brief report, we show that G2C4 ...
Source: Acta Neuropathologica - November 29, 2023 Category: Neurology Source Type: research
Microglia activation in periplaque white matter in multiple sclerosis depends on age and lesion type, but does not correlate with oligodendroglial loss
AbstractMultiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the CNS. The disease course in MS is highly variable and driven by a combination of relapse-driven disease activity and relapse-independent disease progression. The formation of new focal demyelinating lesions is associated with clinical relapses; however, the pathological mechanisms driving disease progression are less well understood. Current concepts suggest that ongoing focal and diffuse inflammation within the CNS in combination with an age-associated failure of compensatory and repair mechanisms contribute to disease progre...
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
Normal meninges harbor oncogenic somatic mutations in meningioma-driver genes
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
Risk of chronic traumatic encephalopathy in rugby union is associated with length of playing career
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
Reply: Soluble oligomers or insoluble fibrils?
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
The neuropathology of intimate partner violence
We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd–8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric cond...
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
Clinical, genomic, and epigenomic analyses of H3K27M-mutant diffuse midline glioma long-term survivors reveal a distinct group of tumors with MAPK pathway alterations
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
Genetical and epigenetical profiling identifies two subgroups of pineal parenchymal tumors of intermediate differentiation (PPTID) with distinct molecular, histological and clinical characteristics
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
Independent prognostic impact of DNA methylation class and chromosome 1p loss in WHO grade 2 and 3 meningioma undergoing adjuvant high-dose radiotherapy: comprehensive molecular analysis of EORTC 22042 –26042
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
PLAG1 fusions extend the spectrum of PLAG(L)-altered CNS tumors
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
Soluble oligomers or insoluble fibrils? Scientific commentary on “Tau seeding and spreading in vivo is supported by both AD-derived fibrillar and oligomeric tau”
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - November 11, 2023 Category: Neurology Source Type: research
Microglia activation in periplaque white matter in multiple sclerosis depends on age and lesion type, but does not correlate with oligodendroglial loss
AbstractMultiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the CNS. The disease course in MS is highly variable and driven by a combination of relapse-driven disease activity and relapse-independent disease progression. The formation of new focal demyelinating lesions is associated with clinical relapses; however, the pathological mechanisms driving disease progression are less well understood. Current concepts suggest that ongoing focal and diffuse inflammation within the CNS in combination with an age-associated failure of compensatory and repair mechanisms contribute to disease progre...
Source: Acta Neuropathologica - October 28, 2023 Category: Neurology Source Type: research
The neuropathology of intimate partner violence
We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd–8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric cond...
Source: Acta Neuropathologica - October 28, 2023 Category: Neurology Source Type: research
Risk of chronic traumatic encephalopathy in rugby union is associated with length of playing career
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 24, 2023 Category: Neurology Source Type: research
PLAG1 fusions extend the spectrum of PLAG(L)-altered CNS tumors
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 23, 2023 Category: Neurology Source Type: research
