Back to Search
Start Over
Seed-competent high-molecular-weight tau species accumulates in the cerebrospinal fluid of Alzheimer's disease mouse model and human patients
- Source :
- Annals of neurology. 80(3)
- Publication Year :
- 2016
-
Abstract
- Objective Cerebrospinal fluid (CSF) tau is an excellent surrogate marker for assessing neuropathological changes that occur in Alzheimer's disease (AD) patients. However, whether the elevated tau in AD CSF is just a marker of neurodegeneration or, in fact, a part of the disease process is uncertain. Moreover, it is unknown how CSF tau relates to the recently described soluble high-molecular-weight (HMW) species that is found in the postmortem AD brain and can be taken up by neurons and seed aggregates. Methods We have examined seeding and uptake properties of brain extracellular tau from various sources, including interstitial fluid (ISF) and CSF from an AD transgenic mouse model and postmortem ventricular and antemortem lumbar CSF from AD patients. Results We found that brain ISF and CSF tau from the AD mouse model can be taken up by cells and induce intracellular aggregates. Ventricular CSF from AD patients contained a rare HMW tau species that exerted a higher seeding activity. Notably, the HMW tau species was also detected in lumbar CSF from AD patients, and its levels were significantly elevated compared to control subjects. HMW tau derived from CSF of AD patients was seed competent in vitro. Interpretation These findings suggest that CSF from an AD brain contains potentially bioactive HMW tau species, giving new insights into the role of CSF tau and biomarker development for AD. Ann Neurol 2016;80:355–367
- Subjects :
- 0301 basic medicine
Genetically modified mouse
Male
Pathology
medicine.medical_specialty
Mice, Transgenic
tau Proteins
Article
03 medical and health sciences
Mice
0302 clinical medicine
Cerebrospinal fluid
Interstitial fluid
Alzheimer Disease
Extracellular
Medicine
Animals
Humans
Aged
business.industry
Neurodegeneration
food and beverages
Brain
Extracellular Fluid
Middle Aged
medicine.disease
In vitro
030104 developmental biology
Neurology
Biomarker (medicine)
Female
Neurology (clinical)
business
030217 neurology & neurosurgery
Intracellular
Biomarkers
Subjects
Details
- ISSN :
- 15318249
- Volume :
- 80
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Annals of neurology
- Accession number :
- edsair.doi.dedup.....6e7f496eedf69eedf586df046d834fcb