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Cited by 94Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Detection of Alzheimer Disease (AD)-Specific Tau Pathology in AD and NonAD Tauopathies by Immunohistochemistry With Novel Conformation-Selective Tau Antibodies

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Gibbons, Garrett S, Banks, Rachel A, Kim, Bumjin, Changolkar, Lakshmi, Riddle, Dawn M, Leight, Susan N, Irwin, David J, Trojanowski, John Q +1 more·2018·Journal of Neuropathology & Experimental Neurology
DOI 10.1093/jnen/nly010PMC PMC6251598
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Abstract

Aggregation of tau into fibrillar structures within the CNS is a pathological hallmark of a clinically heterogeneous set of neurodegenerative diseases termed tauopathies. Unique misfolded conformations of tau, referred to as strains, are hypothesized to underlie the distinct neuroanatomical and cellular distribution of pathological tau aggregates. Here, we report the identification of novel tau monoclonal antibodies (mAbs) that selectively bind to an Alzheimer disease (AD)-specific conformation of pathological tau. Immunohistochemical analysis of tissue from various AD and nonAD tauopathies demonstrate selective binding of mAbs GT-7 and GT-38 to AD tau pathologies and absence of immunoreactivity for tau aggregates that are diagnostic of corticobasal degenerations (CBD), progressive supranuclear palsy (PSP), and Pick's disease (PiD). In cases with co-occurring AD tauopathy, GT-7 and GT-38 distinguish comorbid AD tau from pathological tau in frontotemporal lobar degeneration characterized by tau inclusions (FTLD-Tau), as confirmed by the presence of both 3 versus 4 microtubule-binding repeat isoforms (3R and 4R tau isoforms, respectively), in AD neurofibrillary tangles but not in the tau aggregates of CBD, PSP, or PiD. These findings support the concept of an AD-specific tau strain. The mAbs described here enable the selective detection of AD tau pathology in nonAD tauopathies.

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Authors
Gibbons, G. S., Banks, R. A., Kim, B., Changolkar, L., Riddle, D. M., Leight, S. N., Irwin, D. J., Trojanowski, J. Q., & Lee, V. M. Y.
Affiliations
University of Pennsylvania (US)
Corresponding author
Lee, Virginia M Y
ORCID
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2018-02-05
Volume
77
Issue
3
Pages
216-228
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1093/jnen/nly010
PMC
PMC6251598
OpenAlex
W2793180732
Cited by
94
References
18
Citations by year
2026: 6 · 2025: 6 · 2024: 13 · 2023: 14 · 2022: 5 · 2021: 14 · 2020: 20 · 2019: 13 · 2018: 3
FWCI
8.77
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (AG053036, AG10124, AG17586)
  • Wyncote Foundation
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, tauopathy, tau conformation, neurofibrillary tangles, corticobasal degeneration, progressive supranuclear palsy, Pick's disease, frontotemporal lobar degeneration, tau isoforms, immunohistochemistry
MeSH terms
Adult, Aged, Aged, 80 and over, Alzheimer Disease, Antibodies, Monoclonal, Female, Humans, Immunohistochemistry, Male, Middle Aged, Molecular Conformation, Phosphorylation, Protein Conformation, Supranuclear Palsy, Progressive, Neurofibrillary Tangles, tau Proteins, Protein Isoforms, Pick Disease of the Brain, Tauopathies

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