Divergent CSF alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy
Open accessAbstract
BACKGROUND: Elevated CSF τ is considered a biomarker of neuronal injury in newly developed Alzheimer's disease (AD) and mild cognitive impairment (MCI) criteria. However, previous studies have failed to detect alterations of τ species in other primary tauopathies. We assessed CSF τ protein abnormalities in AD, a tauopathy with prominent Aβ pathology, and progressive supranuclear palsy (PSP), a primary tauopathy characterised by deposition of four microtubule-binding repeat (4R) τ with minimal Aβ pathology. METHODS: 26 normal control (NC), 37 AD, and 24 patients with PSP participated in the study. AD and PSP were matched for severity using the clinical dementia rating sum of boxes (CDR-sb) scores. The INNO BIA AlzBio3 multiplex immunoassay was used to measure CSF Aβ, total τ, and ptau181. Additional, novel ELISAs targeting different N-terminal and central τ epitopes were developed to examine CSF τ components and to investigate interactions between diagnostic group, demographics and genetic variables. RESULTS: PSP had lower CSF N-terminal and C-terminal τ concentrations than NC and AD measured with the novel τ ELISAs and the standard AlzBio3 τ and ptau assays. AD had higher total τ and ptau levels than NC and PSP. There was a gender by diagnosis interaction in AD and PSP for most τ species, with lower concentrations for male compared to female patients. CONCLUSIONS: CSF τ fragment concentrations are different in PSP compared with AD despite the presence of severe τ pathology and neuronal injury in both disorders. CSF τ concentration likely reflects multiple factors in addition to the degree of neuronal injury.
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CSF tau levels are not increased in non-AD tauopathies.
“CSF tau levels are not increased in non-AD tauopathies57–60, suggesting that extracellular tau is not a primary target in these conditions.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [60]
Extracellular tau is not a primary target in non-AD tauopathies.
“CSF tau levels are not increased in non-AD tauopathies57–60, suggesting that extracellular tau is not a primary target in these conditions.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [60]
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- Authors
- Wagshal, D., Sankaranarayanan, S., Guss, V., Hall, T., Berisha, F., Lobach, I., Karydas, A., Voltarelli, L., Scherling, C., Heuer, H., Tartaglia, M. C., Miller, Z., Coppola, G., Ahlijanian, M., Soares, H., Kramer, J. H., Rabinovici, G. D., Rosen, H. J., Miller, B. L., Meredith, J., & Boxer, A. L.
- Affiliations
- University of California, San Francisco (US)
- Bristol-Myers Squibb (United States) (US)
- University of California, Los Angeles (US)
- Corresponding author
- Boxer, A. L.
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2014-06-04
- Volume
- 86
- Issue
- 3
- Pages
- 244-250
- ISSN
- 0022-3050 (ISSN-L)
- PMC
- PMC4256124
- OpenAlex
- W2133759450
- Cited by
- 132
- References
- 47
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 18 · 2023: 5 · 2022: 15 · 2021: 17 · 2020: 7 · 2019: 16 · 2018: 13 · 2017: 14 · 2016: 10 · 2015: 4 · 2014: 3
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Alzheimer's Association (K23-AG031861)
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- Hellman Family Foundation
- TauRx Pharmaceuticals
- Elan
- Kyowa Hakko Kirin
- H. Lundbeck A/S
- National Institutes of Health (AG19724)
- Genentech
- Avid Radiopharmaceuticals
- National Institute on Aging (AG031861, AG23501, R01AG022983, AG-19724, R01AG031278, K23AG031861, K24AG045333, R01AG038791, P01AG019724, R01AG032289, P50AG023501)
- 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 › Parkinson's Disease Mechanisms and Treatments
- Keywords
- tauopathy, Alzheimer's disease, progressive supranuclear palsy, cerebrospinal fluid tau, phosphorylated tau 181, amyloid-beta, 4R tau, sex differences, biomarkers, neuronal injury
- MeSH terms
- Aged, Alzheimer Disease, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Peptide Fragments, Phosphorylation, Prognosis, Reference Values, Supranuclear Palsy, Progressive, Biomarkers, Amyloid beta-Peptides, tau Proteins, Tauopathies, Apolipoprotein E4
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