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Soluble P‐tau217 reflects both amyloid and tau pathology in the human brain and mediates the association of amyloid with neocortical tau
Author(s) -
MattssonCarlgren Niklas,
Janelidze Shorena,
Bateman Randall J.,
Smith Ruben,
Stomrud Erik,
Serrano Geidy E.,
Reiman Eric M.,
Palmqvist Sebastian,
Dage Jeffrey L.,
Beach Thomas G.,
Hansson Oskar
Publication year - 2021
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.050391
Subject(s) - tangle , amyloid (mycology) , neurofibrillary tangle , dementia , pathology , tau pathology , alzheimer's disease , temporal lobe , cohort , β amyloid , medicine , disease , psychology , neuroscience , senile plaques , mathematics , pure mathematics , epilepsy
Background Alzheimer’s disease is characterized by β‐amyloid plaques and tau tangles. Plasma levels of phospho‐tau217 (P‐tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β‐amyloid plaque accumulation, tau tangle accumulation, or both. Method We studied plasma P‐tau217 in a cohort with post‐mortem neuropathological data (N=88), for correlations with plaque and tangle density, and in a cohort with β‐amyloid and tau PET imaging (“BioFINDER‐2”, N=426). Result In the cohort with post‐mortem neuropathological data, both plaque and tangle density contributed independently to higher P‐tau217 (Fig 1). Several findings were replicated in the cohort with PET imaging, where β‐amyloid and tau PET were independently associated to P‐tau217. P‐tau217 correlated with β‐amyloid PET (but not tau PET) in early disease stages, and with both β‐amyloid and (more strongly) tau PET in late disease stages (Fig 2). Finally, P‐tau217 mediated the association between β‐amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe (Fig 3). Conclusion These findings support the hypothesis that plasma P‐tau217 is associated with both β‐amyloid plaques and tau tangles and is congruent with the hypothesis that P‐tau is involved in β‐amyloid‐dependent formation of neocortical tau tangles (Fig 4).