Neuroimaging studies of hippocampal volumes in patients with amyotrophic lateral sclerosis (ALS) have reported inconsistent results. Our aims were to demonstrate that such discrepancies are largely due to atrophy of different regions of the hippocampus that emerge in different disease stages of ALS and to explore the existence of co-pathology in ALS patients. We used the well-validated King's clinical staging system for ALS to classify patients into different disease stages. We investigated in vivo hippocampal atrophy patterns across subfields and anterior-posterior segments in different King's stages using structural MRI in 76 ALS patients and 94 health controls (HCs). The thalamus, corticostriatal tract and perforant path were used as structural controls to compare the sequence of alterations between these structures and the hippocampal subfields. Compared with HCs, ALS patients at King's stage 1 had lower volumes in the bilateral posterior subiculum and presubiculum; ALS patients at King's stage 2 exhibited lower volumes in the bilateral posterior subiculum, left anterior presubiculum and left global hippocampus; ALS patients at King's stage 3 showed significantly lower volumes in the bilateral posterior subiculum, dentate gyrus and global hippocampus. Thalamic atrophy emerged at King's stage 3. White matter tracts remained normal in a subset of ALS patients. Our study demonstrated that the pattern of hippocampal atrophy in ALS patients varies greatly across King's stages. Future studies in ALS patients that focus on the hippocampus may help to further clarify possible co-pathologies in ALS.
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http://dx.doi.org/10.1016/j.nicl.2021.102816 | DOI Listing |
J Neural Transm (Vienna)
January 2025
Neurology Department, LR18SP03, Razi University Hospital, Tunis, Tunisia.
Amyotrophic Lateral Sclerosis(ALS) has traditionally been managed as a neuromuscular disorder. However, recent evidence suggests involvement of non-motor domains. This study aims to evaluate the impact of APOE and MAPT genotypes on the cognitive features of ALS.
View Article and Find Full Text PDFBackground: Inclusions of TAR DNA binding protein of 43kDa (TDP-43) constitute the main characteristic pathology in the majority (∼97%) of amyotrophic lateral sclerosis (ALS) cases and approximately 50% of patients with frontotemporal lobar degeneration (FTLD). TDP-43 is a nuclear RNA binding protein; however, in disease, it becomes hyperphosphorylated and/or insoluble, hindering its nuclear function in maintaining RNA homeostasis. Importantly, the incidence of TDP-43 proteinopathy extends to aging brains (LATE) and may be concomitant with Alzheimer's disease (AD) neuropathological changes (LATE/AD) in up to 70% of AD patients.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Background: Glaucoma is characterized by progressive optic nerve degeneration that results in irreversible blindness, and it can be considered a neurodegenerative disorder of both the eye and the brain. Increasing evidence suggest that glaucoma shares some common neurodegenerative pathways with Frontotemporal Lobar Degeneration (FTLD), Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's Disease (AD) among others. Interestingly, a recent study revealed the presence of abnormal TAR DNA-binding protein 43 (TDP-43) inclusions and aggregates in retinal ganglion cells and other retinal cell types in FTLD-TDP patients; however, the significance of this pathology and its impact on retinal function and optical nerve integrity is unknown.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Barrow Neurological Institute, Phoenix, AZ, USA; Arizona State University, Tempe, AZ, USA.
Background: TDP-43 is an RNA binding protein that is a pathological hallmark of multiple neurodegenerative diseases including Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). The frequency of observed TDP-43 pathology is estimated at 97% in ALS, 45% in FTD and 40-57% in AD and is characterized by a mislocalization of TDP-43 from the nucleus to the cytoplasm. Indeed, TDP-43 is the third most common proteinopathy in AD, behind only Amyloid beta and Tau.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurology, Columbia University, New York, NY, USA.
Background: Lipid dysregulation is a known feature of Alzheimer's Disease. Importantly, alterations in lipids pathways affect immune responses in cells like microglia, which have been shown to accumulate cholesterol in both aging and neurodegeneration. Recently, the presence of TDP-43 inclusions has been linked to increased severity of cognitive impairment in AD patients.
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