Four subgroups based on tau levels in Alzheimer's disease observed in two independent cohorts
: Duits Flora H, Wesenhagen Kirsten EJ, Ekblad Laura, Wolters Emma, Willemse Eline AJ, Scheltens Philip, van der Flier Wiesje M, Teunissen Charlotte E, Visser Ppieter Jelle, Tijms Betty M
Publisher: BMC
: 2021
Alzheimer's Research and Therapy
: ALZHEIMERS RESEARCH & THERAPY
: ALZHEIMERS RES THER
: ARTN 2
: 13
: 1
: 25
: 1758-9193
DOI: https://doi.org/10.1186/s13195-020-00713-3
: https://research.utu.fi/converis/portal/detail/Publication/53303602
BackgroundAs 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.MethodsWe 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).ResultsIndividuals 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).LimitationsThe number of subjects in some subgroups and subanalyses was small, especially in the highest tau subgroup and in tau PET analyses.ConclusionsIn 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.
Alzheimer's disease, CSF tau, Gaussian mixture modelling
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