Four subgroups based on tau levels in Alzheimer's disease observed in two independent cohorts.

ABSTRACT:

Background

As Alzheimer's disease (AD) pathology presents decades before dementia manifests, unbiased biomarker cut-points may more closely reflect presence of pathology than clinically defined cut-points. Currently, unbiased cerebrospinal fluid (CSF) tau cut-points are lacking.

Methods

We investigated CSF t-tau and p-tau cut-points across the clinical spectrum using Gaussian mixture modelling, in two independent cohorts (Amsterdam Dementia Cohort and ADNI).

Results

Individuals with normal cognition (NC) (total n =?1111), mild cognitive impairment (MCI) (total n =?1213) and Alzheimer's disease dementia (AD) (total n =?1524) were included. In both cohorts, four CSF t- and p-tau distributions and three corresponding cut-points were identified. Increasingly high tau subgroups were characterized by steeper MMSE decline and higher progression risk to AD (cohort/platform-dependent HR, t-tau 1.9-21.3; p-tau 2.2-9.5).

Limitations

The number of subjects in some subgroups and subanalyses was small, especially in the highest tau subgroup and in tau PET analyses.

Conclusions

In two independent cohorts, t-tau and p-tau levels showed four subgroups. Increasingly high tau subgroups were associated with faster clinical decline, suggesting our approach may aid in more precise prognoses.

SUBMITTER: Duits FH 

PROVIDER: S-EPMC7780683 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature