Signature laminar distributions of pathology in frontotemporal lobar degeneration.
Frontotemporal lobar degeneration
Infragranular
Laminar pathology
Supragranular
TDP-43
Tau
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
11
10
2021
accepted:
28
12
2021
revised:
11
12
2021
pubmed:
9
1
2022
medline:
5
4
2022
entrez:
8
1
2022
Statut:
ppublish
Résumé
Frontotemporal lobar degeneration (FTLD) with either tau (FTLD-tau) or TDP-43 (FTLD-TDP) inclusions are distinct proteinopathies that frequently cause similar frontotemporal dementia (FTD) clinical syndromes. FTD syndromes often display macroscopic signatures of neurodegeneration at the level of regions and networks, but it is unclear if subregional laminar pathology display patterns unique to proteinopathy or clinical syndrome. We hypothesized that FTLD-tau and FTLD-TDP accumulate pathology in relatively distinct cortical layers independent of clinical syndrome, with greater involvement of lower layers in FTLD-tau. The current study examined 170 patients with either FTLD-tau (n = 73) or FTLD-TDP (n = 97) spanning dementia and motor phenotypes in the FTD spectrum. We digitally measured the percent area occupied by tau and TDP-43 pathology in upper layers (I-III), lower layers (IV-VI), and juxtacortical white matter (WM) from isocortical regions in both hemispheres where available. Linear mixed-effects models compared ratios of upper to lower layer pathology between FTLD groups and investigated relationships with regions, WM pathology, and global cognitive impairment while adjusting for demographics. We found lower ratios of layer pathology in FTLD-tau and higher ratios of layer pathology in FTLD-TDP, reflecting lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology, respectively (p < 0.001). FTLD-tau displayed lower ratios of layer pathology related to greater WM tau pathology (p = 0.002) and to earlier involved/severe pathology regions (p = 0.007). In contrast, FTLD-TDP displayed higher ratios of layer pathology not related to either WM pathology or regional severity. Greater cognitive impairment was associated with higher ratios of layer pathology in FTLD-tau (p = 0.018), but was not related to ratios of layer pathology in FTLD-TDP. Lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology are proteinopathy-specific, regardless of clinical syndromes or regional networks that define these syndromes. Thus, patterns of laminar change may provide a useful anatomical framework for investigating how degeneration of select cells and corresponding laminar circuits influence large-scale networks and clinical symptomology in FTLD.
Identifiants
pubmed: 34997851
doi: 10.1007/s00401-021-02402-3
pii: 10.1007/s00401-021-02402-3
pmc: PMC8858288
doi:
Substances chimiques
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
363-382Subventions
Organisme : NIA NIH HHS
ID : P01 AG017586
Pays : United States
Organisme : NINDS NIH HHS
ID : R01-NS109260-01A1
Pays : United States
Organisme : NINDS NIH HHS
ID : P50 NS053488
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG066597
Pays : United States
Organisme : NIA NIH HHS
ID : R01-AG038490-01A1
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG062418
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG032953
Pays : United States
Organisme : NIA NIH HHS
ID : R01-AG054519-02
Pays : United States
Organisme : NIA NIH HHS
ID : U19-AG062418-03
Pays : United States
Organisme : NINDS NIH HHS
ID : P50-NS053488-09
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS109260
Pays : United States
Organisme : NIA NIH HHS
ID : P01-AG017586-01
Pays : United States
Organisme : NIA NIH HHS
ID : P01-AG032953
Pays : United States
Organisme : NIA NIH HHS
ID : U01-AG052943-01
Pays : United States
Organisme : NIA NIH HHS
ID : P30-AG10124
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072979
Pays : United States
Informations de copyright
© 2022. The Author(s).
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