Precision diagnosis and staging of TDP-43 proteinopathies: harnessing the power of artificial intelligence

Article Clinical Neurology

Data-driven neuropathological staging and subtyping of TDP-43 proteinopathies

Alexandra L. Young et al.

Summary: Through data-driven disease progression modelling, a fine-grained empirical staging system for TAR DNA-binding protein-43 (TDP-43) proteinopathies has been established, which can accurately classify frontotemporal lobar degeneration due to TDP-43 (FTLD-TDP), amyotrophic lateral sclerosis (ALS) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). The study reveals substantial heterogeneity in the progression patterns of ALS and FTLD-TDP, and highlights the need for further investigation in larger cross-cohort studies.

BRAIN (2023)

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Review Biochemistry & Molecular Biology

Hallmarks of neurodegenerative diseases

David M. Wilson III et al.

Summary: This article presents eight hallmarks of neurodegenerative diseases (NDDs), including pathological protein aggregation, synaptic and neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA and RNA defects, inflammation, and neuronal cell death. These hallmarks and their interactions provide a framework for studying NDDs holistically, which can be used to define pathogenic mechanisms, categorize different NDDs based on their primary hallmarks, stratify patients within a specific NDD, and design multi-targeted, personalized therapies to effectively halt NDDs.

CELL (2023)

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Review Neurosciences

Moving beyond amyloid and tau to capture the biological heterogeneity of Alzheimer's disease

Tracy L. Young-Pearse et al.

Summary: Alzheimer's disease (AD) has a range of cognitive deficits and levels of neuropathology. Genetic studies have identified around 70 associated loci to date, implicating various biological processes that mediate risk for AD. However, most experimental systems for testing new therapeutics do not consider the genetically complex drivers of AD risk.

TRENDS IN NEUROSCIENCES (2023)

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Article Oncology

Pan-cancer integrative histology-genomic analysis via multimodal deep learning

Richard J. Chen et al.

Summary: Computational pathology has shown promise in developing prognostic models based on histology images. This study uses multimodal deep learning to integrate pathology images and molecular profile data, and discover prognostic features that correlate with outcomes.

CANCER CELL (2022)

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Article Clinical Neurology

LATE-NC staging in routine neuropathologic diagnosis: an update

Peter T. Nelson et al.

Summary: This report updates the neuropathologic criteria for diagnosing and staging LATE-NC and provides practical suggestions for integrating genetic information and comorbid pathologies. It also highlights recent research findings that improve differentiation of LATE-NC from other subtypes of TDP-43 pathology and offers guidance for diagnosing unusual cases. Additionally, the report describes the neuroanatomical regions of interest in LATE-NC and specifies the implications for TDP-43 immunohistochemical results. The report emphasizes unresolved questions and areas requiring further study.

ACTA NEUROPATHOLOGICA (2022)

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Article Neurosciences