Plasma P-tau promises diagnostic accuracy and prediction of cognitive decline

Extraordinary advances in plasma tau biomarkers, and especially in P-tau217, offer to aid diagnostic accuracy, enrich clinical trial recruitment and – when used together with brief psychometric tests -- individualize prediction of decline in people with cognitive complaints.

Plasma P-tau differentiates AD dementia from other neurodegenerative disorders and performs as well as CSF markers and PET imaging1 – to the extent that it could in principle be a standalone biomarker when used together with clinical work-up, Oskar Hansson (University of Lund, Sweden) told ADPD 2021 Virtual.

Recent work shows that plasma levels of tau phosphorylated at threonine-217 (P-tau217) are low in people who are amyloid-beta (Aβ) negative, whether or not they are cognitively impaired.1

Plasma P-tau is better than MRI and as good as PET and CSF at distinguishing Alzheimer’s from other dementias

But they are raised in those who are Aβ positive, and increase according to cognitive deficit: the level of P-tau217 is greater in people with mild cognitive impairment (MCI) than in those who are cognitively intact, and levels are higher still in patients with AD dementia.

P-tau217 is not increased in Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy or frontotemporal dementia. And the marker is better at distinguishing AD from non-AD diseases than plasma P-tau181, cortical thickness, hippocampal volume, or the marker of neurodegeneration plasma neurofilament light (NfL).

In making this distinction, it is at least as specific for AD as P-tau in the CSF or tau-PET imaging.

 

Assessing risk of cognitive decline

Plasma tau set to help as a prognostic indicator in people with MCI

In addition to its diagnostic accuracy, plasma tau looks set to become extremely helpful as a prognostic indicator in people with MCI or cognitive complaints.

When combined in a model with NfL, plasma P-tau181 was highly predictive (AUC 0.88) for the development of AD dementia over four years in patients with MCI in the Swedish BioFINDER and ADNI cohorts.2

A further study3 demonstrated that – when used together with brief cognitive tests measuring memory and executive function, and APOE status -- plasma P-tau217 can predict the development of AD dementia in individual non-demented subjects with cognitive complaints. The prognostic algorithm had an AUC of 0.91.

And in participants in the Swedish BioFINDER study, steeper in increase in plasma P-tau217 levels over six years were associated with faster cognitive decline and brain atrophy.4

It seems that soluble P-tau mediates the association between plaques and tangles

MCI patients who later converted to AD dementia had accelerated P-tau217 rise when compared to other people with MCI. P-tau217 did not change in amyloid-β-negative participants.

In people who are cognitively unimpaired, it might be necessary to combine P-tau with plasma Aβ42/Aβ40 ratio to detect Aβ pathology and predict cognitive decline, Professor Hansson said. But it does seem that soluble P-tau mediates the association between plaques and tangles.

 

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Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References

1. Palmqvist S et al. JAMA 2020 July 28 doi:10.1001/jama.2020.12134

2. Cullen NC et al. Nature Aging 2021;1:114-23

3. Palmqvist S et al. Under review

4. Mattsson-Carlgren N et al. Brain 2020; 143: 3234–41

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