Neuropathology of Frontotemporal Lobar Degeneration-Tau (FTLD-Tau)
Open accessAbstract
A clinically and pathologically heterogeneous type of frontotemporal lobar degeneration has abnormal tau pathology in neurons and glia (FTLD-tau). Familial FTLD-tau is usually due to mutations in the tau gene (MAPT). Even FTLD-tau determined by MAPT mutations has clinical and pathologic heterogeneity. Tauopathies are subclassified according to the predominant species of tau that accumulates, with respect to alternative splicing of MAPT, with tau proteins containing three (3R) or four repeats (4R) of ~32 amino acids in the microtubule binding domain. In Pick's disease (PiD), 3R tau predominates, whereas 4R tau is characteristic of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Depending upon the specific mutation in MAPT, familial FTLD-tau can have 3R, 4R or a combination of 3R and 4R tau. PiD is the least common FTLD-tau characterized by neuronal Pick bodies in a stereotypic neuroanatomical distribution. PSP and CBD are more common than PiD and have extensive clinical and pathologic overlap, with no distinctive clinical syndrome or biomarker that permits their differentiation. Diagnosis rests upon postmortem examination of the brain and demonstration of globose tangles, oligodendroglial coiled bodies and tufted astrocytes in PSP or threads, pretangles and astrocytic plaques in CBD. The anatomical distribution of tau pathology determines the clinical presentation of PSP and CBD, as well as PiD. The basis for this selective cortical vulnerability in FTLD-tau is unknown.
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There is considerable molecular and biomarker overlap between CBD, PSP and a subset of FTD.
“Although neuropathologically distinct, there is considerable molecular and biomarker overlap between CBD, PSP and a subset of FTD [13].”
From Shared genetic risk between corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia (2017) · cites this paper as [13]
The ‘Clinical and pathological overlap in 4R tauopathies’ section (page not provided) describes shared 4R tau pathology and genetic risk in CBD and PSP, and says no specific marker differentiates their tau pathology. The Abstract (page not provided) identifies a subset of frontotemporal lobar degeneration as tau-related, but the paper does not establish biomarker overlap across CBD, PSP, and that FTD subset. (LLM, conf=0.82)
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Self-citation
- Authors
- Dickson, D. W., Kouri, N., Murray, M. E., & Josephs, K. A.
- Affiliations
- Mayo Clinic in Florida (US)
- Mayo Clinic (US)
- Corresponding author
- Dickson, Dennis W.
- Venue
- Journal of Molecular Neuroscience
- Published
- 2011-07-01
- Volume
- 45
- Issue
- 3
- Pages
- 384-389
- ISSN
- 0895-8696 (ISSN-L)
- 1559-1166
- PMC
- PMC3208128
- OpenAlex
- W2041390299
- Cited by
- 380
- References
- 6
- Citations by year
- 2026: 25 · 2025: 26 · 2024: 28 · 2023: 33 · 2022: 29 · 2021: 39 · 2020: 27 · 2019: 29 · 2018: 28 · 2017: 35 · 2016: 11 · 2015: 24 · 2014: 13 · 2013: 22 · 2012: 11
- FWCI
- 10.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- National Institutes of Health
- National Institute on Aging (P50 AG25711, R21-AG38736, P50‐AG16574, P01-AG-17216, R21AG038736, R01‐AG37491, R01AG037491, P50AG025711, P01AG017216, P50AG016574)
- National Institute of Neurological Disorders and Stroke (P50-NS72187, P50NS072187)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- tauopathy, MAPT mutations, tau isoforms, Pick's disease, corticobasal degeneration, progressive supranuclear palsy, Pick bodies, coiled bodies, tufted astrocytes, alternative splicing
- MeSH terms
- Humans, Supranuclear Palsy, Progressive, tau Proteins, Pick Disease of the Brain, Tauopathies, Frontotemporal Lobar Degeneration
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