Frontotemporal lobar degeneration FTLD-tau: preclinical lesions, vascular, and Alzheimer-related co-pathologies
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Frontotemporal lobar degeneration with τ pathology (FTLD-tau) is one of a group of neurodegenerative diseases that manifests with cognitive decline. Alzheimer (AD) and cerebrovascular lesions are commonly noted in the brains of most elderly individuals, begging the question as to whether (a) coexisting AD and vascular pathology or age contribute to the development of FTLD-tau disorders and vice versa and (b) FTLD-tau-like pathology can be found in non-diseased individuals. We studied brains of FTLD-tau cases exhibiting (a) argyrophilc grain disease (AGD), (b) progressive supranuclear palsy (PSP), (c) corticobasal degeneration (CBD), or (d) Pick's disease (PiD) for coexisting AD and vascular pathology for comparison with that of non-diseased individuals and AD patients. We confirmed that AGD lowered the threshold for AD pathology to cause dementia. Such an effect was not seen in PSP, CBD, or PiD. In PiD, white matter degeneration and demyelination was observed in the frontal and temporal lobes in association with small vessel disease (SVD)-related changes in white matter arteries. Age at death varied among the four types of FTLD-tau. PiD cases were youngest at death followed by CBD, PSP, and finally AGD. In 9.8% of non-diseased controls, we found grains, coiled bodies, and/or τ-positive astrocytes mimicking an AGD-like pattern. Moreover, the prevalence of FTLD-tau pathology in non-diseased individuals increased with age. In summary, this study demonstrates that age impacts of the diversity of neuropathological changes in FTLD-tau. The age-related coexistence of AD-related pathology is, thereby, associated with AGD but not with PSP, CBD, and PiD. Moreover, severe SVD and white matter demyelination is associated with PiD indicating a role of vascular copathology in this type of FTLD-tau. Finally, our finding that FTLD-tau-related pathological lesions occur in non-diseased individuals suggests that preclinical stages of FTLD-tau exist. As such, our results indicate that age, together with vascular and AD-related copathology, contributes to the morphological appearance of FTLD-tau.
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White matter changes such as white matter atrophy and the occurrence of white matter hyperintensities have been reported.
“In addition, white matter changes such as white matter atrophy and the occurrence of white matter hyperintensities have been reported [9].”
From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [9]
The Results section ('Cerebral vessel pathology and vascular lesions in FTLD-tau and AD'; page unavailable) reports white matter lesions and, in Pick’s disease, white matter degeneration and demyelination. It does not report white matter atrophy or white matter hyperintensities specifically; searches for those terms found no supporting passage in our copy. (LLM, conf=0.85)
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- Authors
- Thal, D. R., von Arnim, C. A. F., Griffin, W. S. T., Mrak, R. E., Walker, L., Attems, J., & Arzberger, T.
- Affiliations
- Universität Ulm (DE)
- University of Arkansas Medical Center (US)
- University of Toledo (US)
- Newcastle University (GB)
- Institut für Neuropathologie (DE)
- Corresponding author
- Thal, Dietmar Rudolf
- Venue
- Journal of Neural Transmission
- Published
- 2015-01-04
- Volume
- 122
- Issue
- 7
- Pages
- 1007-1018
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- PMC
- PMC6655426
- OpenAlex
- W2073249623
- Cited by
- 67
- References
- 6
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 10 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 2
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Lirias (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- Alzheimer Society
- Newcastle University
- Bundesministerium für Bildung und Forschung
- Newcastle upon Tyne Hospitals NHS Foundation Trust
- KWF Kankerbestrijding (13803)
- National Institutes of Health
- Medical Research Council (G0400074, MR/L016451/1)
- National Institute on Aging (P01AG012411)
- 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
- argyrophilic grain disease, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, Alzheimer's disease co-pathology, cerebral small vessel disease, white matter demyelination, age at death, coiled bodies
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Brain, Cerebrovascular Disorders, Female, Humans, Male, Middle Aged, Cohort Studies, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Young Adult, Frontotemporal Lobar Degeneration
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