Neuropathological spectrum of anti-IgLON5 disease and stages of brainstem tau pathology: updated neuropathological research criteria of the disease-related tauopathy.
3R
4R tau
ALS
Anti-IgLON5 disease
Anti-IgLON5 tauopathy
Atypical
Brainstem tauopathy
Dementia
IgLON5
Motor neuron disease
Neuropathology
PSP
Stages
TDP-43
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
14 Oct 2024
14 Oct 2024
Historique:
received:
16
04
2024
accepted:
12
09
2024
revised:
23
08
2024
medline:
14
10
2024
pubmed:
14
10
2024
entrez:
14
10
2024
Statut:
epublish
Résumé
Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers. In 15 patients (68%), we observed a hypothalamic and brainstem-predominant tauopathy of varying severity in which the original research neuropathological criteria were readily applicable. This pathology was observed in younger patients (median age at onset 61 years) with a long disease duration (median 9 years). In contrast, in 7 (32%) patients, the originally described brainstem tauopathy was nearly absent or only minimal in the form of delicate threads, despite mild-to-moderate neurodegenerative features, consistent clinical symptoms and the presence of anti-IgLON5 antibodies in CSF and serum. These patients were older at onset (median 79 years) and had shorter disease duration (median < 1 year). Overall, about one-third of the patients showed concomitant TDP-43 pathology within the regions affected by tau pathology and/or neurodegeneration. Based on these observations and in view of the spectrum of the tau burden in the core regions involved in the disease, we propose a simple staging system: stage 1 mild neurodegeneration without overt or only minimal tau pathology, stage 2 moderate neurodegeneration and mild/ moderate tauopathy and stage 3 prominent neurodegeneration and tau pathology. This staging intends to reflect a potential (age- and time-dependent) progression of tau pathology, supporting the current notion that tau accumulation is a secondary phenomenon related to the presence of anti-IgLON5 antibodies in the CNS. Finally, we adapt the original research criteria of the anti-IgLON5 disease-related tauopathy to include the spectrum of pathologies observed in this larger postmortem series.
Identifiants
pubmed: 39400557
doi: 10.1007/s00401-024-02805-y
pii: 10.1007/s00401-024-02805-y
doi:
Substances chimiques
IgLON5 protein, human
0
tau Proteins
0
Cell Adhesion Molecules, Neuronal
0
Autoantibodies
0
DNA-Binding Proteins
0
TARDBP protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
53Subventions
Organisme : Austrian Science Fund
ID : SYNABS
Organisme : Austrian Science Fund
ID : I6565-B
Organisme : Austrian Science Fund
ID : T996-B30
Organisme : Bundesministerium für Bildung und Forschung
ID : 01GM2208B
Organisme : Bundesministerium für Bildung und Forschung
ID : 01GM2208A
Organisme : Instituto de Salud Carlos III
ID : PI21/00165
Organisme : Instituto de Salud Carlos III
ID : PI21/00165
Organisme : Horizon 2020 Framework Programme
ID : N° 825575
Organisme : Tekniikan Akatemia
ID : 341007
Organisme : Helsingin Yliopisto
ID : TYH2022316
Informations de copyright
© 2024. The Author(s).
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