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Comparison of cerebrospinal fluid phosphorylated tau 181 and 217 for cognitive progression
Author(s) -
Mielke Michelle M.,
Aakre Jeremiah A.,
AlgecirasSchimnic Alicia,
Proctor Nicholas,
Machulda Mary M.,
Knopman David S.,
Jack Clifford R.,
Petersen Ronald C.,
Dage Jeffrey L.
Publication year - 2020
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 - 10.1002/alz.040503
Subject(s) - cerebrospinal fluid , medicine , dementia , cognitive impairment , oncology , cognitive decline , apolipoprotein e , gastroenterology , psychology , disease
Background A previous study demonstrated that cerebrospinal fluid (CSF) phosphorylated tau 217 (pTau217), compared to phosphorylated tau 181 (pTau181), correlated more strongly with Tau PET and was better able to distinguish between AD and non‐AD neurodegenerative diseases. The aim of this study was to compare these two CSF tau markers for cognitive progression. Method We included 666 cognitively unimpaired (CU) and 89 mild cognitive impairment (MCI) Mayo Clinic Study on Aging community‐based participants (mean age of 71.6 years) with CSF amyloid and tau measurements. CSF amyloid‐beta 42 (Aβ42) was measured with automated electrochemiluminescence Elecsys immunoassays (Roche Diagnostics); a cut‐off of <1026 pg/ml was considered amyloid positive (A+). CSF pTau181 and pTau217 were measured with the Mesoscale discovery platform (MSD). Cutoffs of pTau181≥217 pg/ml and pTau217≥288 pg/ml were considered tau positive (T+). Cox proportional hazards models with time as the time scale were used to examine the relationship between the CSF markers and progression from CU to MCI and MCI to dementia. Covariates included age, sex, education, and APOE. Result Tau positivity (T+) based on pTau217 (HR = 2.45, 95% CI: 1.45, 4.11) was a greater risk factor for incident MCI compared to pTau181 (HR = 2.07, 95% CI: 1.19, 3.61). Among individuals who were A+T+, T+ based on pTau217 (HR = 3.01, 95% CI: 1.66‐5.45) was a greater risk factor of incident MCI than pTau181 (2.80, 95% CI: 1.48, 5.31). Among the 89 MCI participants, T+ based on pTau217 was a much greater risk factor for dementia (HR = 4.92, 95% CI: 1.37, 17.61) than pTau181 (HR = 1.55, 95% CI: 0.43‐5.55). Conclusion CSF pTau217 is a better marker of cognitive progression, especially from MCI to dementia, compared to CSF pTau181.