Differential vulnerability of the dentate gyrus to tauopathies in dementias.
Dentate gyrus
Frontotemporal lobar degeneration
Primary progressive aphasia
Tauopathy
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
03 01 2023
03 01 2023
Historique:
received:
21
11
2022
accepted:
23
11
2022
entrez:
3
1
2023
pubmed:
4
1
2023
medline:
6
1
2023
Statut:
epublish
Résumé
The dentate gyrus (DG), a key hippocampal subregion in memory processing, generally resists phosphorylated tau accumulation in the amnestic dementia of the Alzheimer's type due to Alzheimer's disease (DAT-AD), but less is known about the susceptibility of the DG to other tauopathies. Here, we report stereologic densities of total DG neurons and tau inclusions in thirty-two brains of human participants with autopsy-confirmed tauopathies with distinct isoform profiles-3R Pick's disease (PiD, N = 8), 4R corticobasal degeneration (CBD, N = 8), 4R progressive supranuclear palsy (PSP, N = 8), and 3/4R AD (N = 8). All participants were diagnosed during life with primary progressive aphasia (PPA), an aphasic clinical dementia syndrome characterized by progressive deterioration of language abilities with spared non-language cognitive abilities in early stages, except for five patients with DAT-AD as a comparison group. 51% of total participants were female. All specimens were stained immunohistochemically with AT8 to visualize tau pathology, and PPA cases were stained for Nissl substance to visualize neurons. Unbiased stereological analysis was performed in granule and hilar DG cells, and inclusion-to-neuron ratios were calculated. In the PPA group, PiD had highest mean total (granule + hilar) densities of DG tau pathology (p < 0.001), followed by CBD, AD, then PSP. PPA-AD cases showed more inclusions in hilar cells compared to granule cells, while the opposite was true in PiD and CBD. Inclusion-to-neuron ratios revealed, on average, 33% of all DG neurons in PiD cases contained a tau inclusion, compared to ~ 7% in CBD, 2% in AD, and 0.4% in PSP. There was no significant difference between DAT-AD and PPA-AD pathologic tau burden, suggesting that differences in DG burden are not specific to clinical phenotype. We conclude that the DG is differentially vulnerable to pathologic tau accumulation, raising intriguing questions about the structural integrity and functional significance of hippocampal circuits in neurodegenerative dementias.
Identifiants
pubmed: 36597124
doi: 10.1186/s40478-022-01485-7
pii: 10.1186/s40478-022-01485-7
pmc: PMC9811688
doi:
Substances chimiques
tau Proteins
0
Types de publication
Journal Article
Research Support, U.S. Gov't, P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1Subventions
Organisme : NIA NIH HHS
ID : R01 AG056258
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC008552
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072977
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG062566
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NIA NIH HHS
ID : K08 AG065463
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS075075
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS047987
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS085770
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG077444
Pays : United States
Informations de copyright
© 2023. The Author(s).
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