Reassessment of Neuronal Tau Distribution in Adult Human Brain and Implications for Tau Pathobiology.

Adult Alzheimer Disease / pathology Brain / pathology Humans Neurofibrillary Tangles / pathology Neurons / metabolism tau Proteins / metabolism
Alzheimer’s disease Brain Distribution Human Neuronal Tau Tauopathy

Journal

Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673

Informations de publication

Date de publication:
28 06 2022
Historique:
received: 21 04 2022
accepted: 10 06 2022
entrez: 28 6 2022
pubmed: 29 6 2022
medline: 1 7 2022
Statut: epublish

Résumé

Tau is a predominantly neuronal, soluble and natively unfolded protein that can bind and stabilize microtubules in the central nervous system. Tau has been extensively studied over several decades, especially in the context of neurodegenerative diseases where it can aberrantly aggregate to form a spectrum of pathological inclusions. The presence of tau inclusions in the form of neurofibrillary tangles, neuropil threads and dystrophic neurites within senile plaques are essential and defining features of Alzheimer's disease. The current dogma favors the notion that tau is predominantly an axonal protein, and that in Alzheimer's disease there is a redistribution of tau towards the neuronal soma that is associated with the formation of pathological inclusions such as neurofibrillary tangles and neuropil threads. Using novel as well as previously established highly specific tau antibodies, we demonstrate that contrary to this overwhelmingly accepted fact, as asserted in numerous articles and reviews, in adult human brain, tau is more abundant in cortical gray matter that is enriched in neuronal soma and dendrites compared to white matter that is predominantly rich in neuronal axons. Additionally, in Alzheimer's disease tau pathology is significantly more abundant in the brain cortical gray matter of affected brain regions compared to the adjacent white matter regions. These findings have important implications for the biological function of tau as well as the mechanisms involved in the progressive spread of tau associated with the insidious nature of Alzheimer's disease.

Identifiants

DOI: 10.1186/s40478-022-01394-9 PMID: 35765058 PMC: PMC9237980
pubmed: 35765058
doi: 10.1186/s40478-022-01394-9
pii: 10.1186/s40478-022-01394-9
pmc: PMC9237980
doi:

Substances chimiques

tau Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

94

Subventions

Organisme : NIA NIH HHS
ID : P30 AG066506
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047266
Pays : United States
Organisme : NIA NIH HHS
ID : P50AG047266
Pays : United States
Organisme : NIA NIH HHS
ID : P30AG066506
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Giavanna Paterno (G)

Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, BMS J483/CTRND, 1275 Center Drive, Gainesville, FL, 32610, USA.

Brach M Bell (BM)

Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, BMS J483/CTRND, 1275 Center Drive, Gainesville, FL, 32610, USA.

Kimberly-Marie M Gorion (KM)

Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, BMS J483/CTRND, 1275 Center Drive, Gainesville, FL, 32610, USA.

Stefan Prokop (S)

Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, BMS J483/CTRND, 1275 Center Drive, Gainesville, FL, 32610, USA.
College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.
Department of Pathology, University of Florida, Gainesville, FL, 32610, USA.
Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, 32610, USA.

Benoit I Giasson (BI)

Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, 32610, USA. bgiasson@ufl.edu.
Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, BMS J483/CTRND, 1275 Center Drive, Gainesville, FL, 32610, USA. bgiasson@ufl.edu.
College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA. bgiasson@ufl.edu.

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