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J Neurol Neurosurg Psychiatry. 2015 Mar;86(3):244-50. doi: 10.1136/jnnp-2014-308004. Epub 2014 Jun 4.

Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy.

Author information

1
Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
2
Bristol-Myers Squibb, Wallingford, Connecticut, USA.
3
Kyowa Hakko Kirin Pharma, Inc., Princeton, New Jersey, USA.
4
Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA Tanz Center for Research in Neurodegenerative disease, University of Toronto, Toronto, Canada.
5
Department of Psychiatry, Semel Institute, University of California, Los Angeles, Los Angeles, California, USA.

Abstract

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.

KEYWORDS:

Alzheimer's Disease; CSF

PMID:
24899730
PMCID:
PMC4256124
DOI:
10.1136/jnnp-2014-308004
[Indexed for MEDLINE]
Free PMC Article

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