Neuropathological associations of limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) differ between the oldest-old and younger-old

Wang, Shih‐Hsiu J.; Guo, Yuanyuan; Ervin, John F.; Lusk, Jay B; Luo, Sheng

doi:10.1007/s00401-022-02432-5

Cited by 14 publications

(11 citation statements)

References 44 publications

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“…Previous studies have employed differing criteria to evaluate vascular pathology, resulting in conflicting results on its relation with HS 5,12,34,37–40 . Despite this lack of consensus, our results support the reported association of arteriolosclerosis with HS 41,42 , as well as with LATE 43,44 . A future consensual evaluation of α-synuclein and vascular pathologies throughout several cohorts would aid the clear delimitation of their relationship with HS progression.…”

Section: Discussionsupporting

confidence: 83%

“…Despite this lack of consensus, our results support the reported association of arteriolosclerosis with HS 41,42 , as well as with LATE 43,44 . A future consensual evaluation of α-synuclein and vascular pathologies throughout several cohorts would aid the clear delimitation of their relationship with HS progression.…”

Section: Discussionsupporting

confidence: 82%

“…(A) amygdala and anterior entorhinal cortex (section corresponding to levels 24-27 of the microatlas by Mai et al 30 ), (B) hippocampal head (levels [32][33][34][35], and (C) hippocampal body immediately posterior to the tip of the uncus (levels [39][40][41][42][43]. Five stages of HS were defined based on qualitative evaluation of H/E histological sections from blocks (B) and (C), resulting in stages at the hippocampal head and body, respectively.…”

Section: Histological Assessment Of the Hippocampusmentioning

confidence: 99%

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A novel histological staging of hippocampal sclerosis that is evident in grey matter lossin vivo

Ortega-Cruz

Uceda-Heras

Iglesias

et al. 2022

Preprint

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INTRODUCTION: Hippocampal sclerosis of aging (HS) is defined by end-stage histological findings, strongly associated with limbic-predominant age-related TDP-43 encephalopathy (LATE). We aimed to characterize features of early HS to refine the understanding of its role within combined pathology. METHODS: We studied 159 brain donations from the multimodal Vallecas Alzheimers Center Study. A staging system (0 to IV) was developed to account for HS progression and analyzed in relation to pre-mortem cognitive and MRI data. RESULTS: Our HS staging system displayed a significant correlation with disease duration, cognitive performance and combined neuropathologies, especially with LATE. Two-level assessment along the hippocampal longitudinal axis revealed an anterior-posterior gradient of HS severity. In vivo MRI showed focally reduced hippocampal grey matter density as a function of HS staging. DISCUSSION: The association of this staging system with clinical progression and structural differences supports its utility in the characterization and potential in vivo monitoring of HS.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 82%

Section: Histological Assessment Of the Hippocampusmentioning

confidence: 99%

See 1 more Smart Citation

A novel histological staging of hippocampal sclerosis that is evident in grey matter lossin vivo

Ortega-Cruz

Uceda-Heras

Iglesias

et al. 2022

Preprint

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“…It has been recognized for over a decade that TDP-43 pathology is often comorbid with ADNC, Lewy body pathology, or both [ 8 , 10 , 46 , 66 , 67 ]. However, these pathologic features also are commonly seen—even when quite severe—in the absence of each other [ 51 , 52 , 88 , 113 , 147 , 153 , 154 ], so they are at least partly independent. Many studies have demonstrated that LATE-NC is associated with additive cognitive impairment for a given amount of other pathologic changes [ 4 , 16 , 17 , 72 , 103 , 111 , 127 ].…”

Section: Late-nc: Recommendations For Pathological Stagingmentioning

confidence: 99%

“…The disease was designated “limbic-predominant age-related TDP-43 encephalopathy” (LATE) [ 114 ], and guidelines were suggested for post-mortem evaluation and staging of LATE neuropathologic changes (LATE-NC). This terminology has been adopted widely [ 16 , 25 , 48 , 50 – 52 , 57 , 74 , 81 , 95 , 100 , 132 , 135 , 138 , 153 ]. However, diagnostic ambiguities and criticisms of the staging scheme have emerged [ 22 , 61 , 115 ].…”

Section: Introductionmentioning

confidence: 99%

LATE-NC staging in routine neuropathologic diagnosis: an update

et al. 2022

Self Cite

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An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer’s disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.

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A novel histological staging of hippocampal sclerosis that is evident in gray matter loss in vivo

Ortega-Cruz

Uceda-Heras

Iglesias

et al. 2023

Alzheimer's & Dementia

View full text Add to dashboard Cite

Introduction: Hippocampal sclerosis of aging (HS) is defined by end-stage histological findings, strongly associated with limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE). We aimed to characterize features of early HS to refine the understanding of its role within combined pathology. Methods:We studied 159 brain donations from the multimodal Vallecas Alzheimer's Center Study. A staging system (0 to IV) was developed to account for HS progression and analyzed in relation to pre-mortem cognitive and magnetic resonance imaging (MRI) data.Results: Our HS staging system displayed a significant correlation with disease duration, cognitive performance, and combined neuropathologies, especially with LATE. Two-level assessment along the hippocampal longitudinal axis revealed an anteriorposterior gradient of HS severity. In vivo MRI showed focally reduced hippocampal gray matter density as a function of HS staging. Discussion:The association of this staging system with clinical progression and structural differences supports its utility in the characterization and potential in vivo monitoring of HS.

show abstract

Neuropathological associations of limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) differ between the oldest-old and younger-old

Cited by 14 publications

References 44 publications

A novel histological staging of hippocampal sclerosis that is evident in grey matter lossin vivo

A novel histological staging of hippocampal sclerosis that is evident in grey matter lossin vivo

LATE-NC staging in routine neuropathologic diagnosis: an update

A novel histological staging of hippocampal sclerosis that is evident in gray matter loss in vivo

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