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Learnings about the complexity of extracellular tau aid development of a blood‐based screen for Alzheimer's disease
Author(s) -
Chen Zhicheng,
Mengel David,
Keshavan Ashvini,
Rissman Robert A.,
Billinton Andrew,
Perkinton Michael,
PercivalAlwyn Jennifer,
Schultz Aaron,
Properzi Michael,
Johnson Keith,
Selkoe Dennis J.,
Sperling Reisa A.,
Patel Purvish,
Zetterberg Henrik,
Galasko Douglas,
Schott Jonathan M.,
Walsh Dominic M.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.09.010
Subject(s) - cerebrospinal fluid , biomarker , cohort , tau protein , disease , alzheimer's disease , medicine , cognitive impairment , cognitive decline , extracellular , oncology , pathology , dementia , chemistry , biochemistry
The tau protein plays a central role in Alzheimer's disease (AD), and there is huge interest in measuring tau in blood and cerebrospinal fluid (CSF). Methods We developed a set of immunoassays to measure tau in specimens from humans diagnosed based on current best clinical and CSF biomarker criteria. Results In CSF, mid‐region‐ and N‐terminal‐detected tau predominated and rose in disease. In plasma, an N‐terminal assay (NT1) detected elevated levels of tau in AD and AD‐mild cognitive impairment (MCI). Plasma NT1 measurements separated controls from AD‐MCI (area under the curve [AUC] = 0.88) and AD (AUC = 0.96) in a discovery cohort and in a Validation Cohort (with AUCs = 0.79 and 0.75, respectively). Discussion The forms of tau in CSF and plasma are distinct, but in each specimen type, the levels of certain fragments are increased in AD. Measurement of plasma NT1 tau should be aggressively pursued as a potential blood‐based screening test for AD/AD‐MCI.