Soluble P‐tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau
Top Cited Papers
Open Access
- 5 May 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 13 (6), e14022
- https://doi.org/10.15252/emmm.202114022
Abstract
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. In a cohort with post‐mortem neuropathological data (N = 88), both plaque and tangle density contributed independently to higher P‐tau217, but P‐tau217 was not elevated in patients with non‐Alzheimer’s disease tauopathies (N = 9). Several findings were replicated in a cohort with PET imaging (“BioFINDER‐2”, N = 426), where β‐amyloid and tau PET were independently associated with P‐tau217. P‐tau217 concentrations 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. Finally, P‐tau217 mediated the association between β‐amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P‐tau217 concentration is increased by 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.Keywords
Funding Information
- National Institute of Neurological Disorders and Stroke (U24 NS072026)
- National Institute on Aging (P30 AG19610)
- Michael J. Fox Foundation for Parkinson's Research
This publication has 22 references indexed in Scilit:
- Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer diseaseNeurology, 2019
- Predicting diagnosis and cognition with 18F‐AV‐1451 tau PET and structural MRI in Alzheimer's diseaseAlzheimer's & Dementia, 2019
- Blood-based biomarkers for Alzheimer disease: mapping the road to the clinicNature Reviews Neurology, 2018
- NIA‐AA Research Framework: Toward a biological definition of Alzheimer's diseaseAlzheimer's & Dementia, 2018
- CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysisThe Lancet Neurology, 2016
- Increased CSF Aβ during the very early phase of cerebral Aβ deposition in mouse modelsEMBO Molecular Medicine, 2015
- The Evolution of Preclinical Alzheimer’s Disease: Implications for Prevention TrialsNeuron, 2014
- Primary age-related tauopathy (PART): a common pathology associated with human agingActa Neuropathologica, 2014
- Editorial on Consensus Recommendations for the Postmortem Diagnosis of Alzheimer Disease from the National Institute on Aging and the Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer DiseaseJournal of Neuropathology and Experimental Neurology, 1997
- The Consortium to Establish a Registry for Alzheimer's Disease (CERAD)Neurology, 1991