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Frontotemporal lobar degeneration FTLD-tau: preclinical lesions, vascular, and Alzheimer-related co-pathologies

Lookup NU author(s): Dr Lauren WalkerORCiD, Professor Johannes Attems


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Frontotemporal lobar degeneration with tau 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 tau-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.

Publication metadata

Author(s): Thal DR, von Arnim CAF, Griffin WST, Mrak RE, Walker L, Attems J, Arzberger T

Publication type: Article

Publication status: Published

Journal: Journal of Neural Transmission

Year: 2015

Volume: 122

Issue: 7

Pages: 1007-1018

Print publication date: 01/07/2015

Online publication date: 04/01/2015

Acceptance date: 22/12/2014

ISSN (print): 0300-9564

ISSN (electronic): 1435-1463

Publisher: Springer


DOI: 10.1007/s00702-014-1360-6


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Funder referenceFunder name
BMBF-(ministry of science and technology) Grant FTLDc
Brains for Dementia research
Biomedical Research Unit for Lewy body dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust
National Institute for Health Research (NIHR) Biomedical Research Centre for Ageing and Age-related disease
13803Alzheimer Forschung Initiative (AFI)
G0400074UK Medical Research Council
R:CH/ML/0712Newcastle University