TY - JOUR
T1 - Four subgroups based on tau levels in Alzheimer’s disease observed in two independent cohorts
AU - Duits, Flora H.
AU - Wesenhagen, Kirsten E. J.
AU - Ekblad, Laura
AU - Wolters, Emma
AU - Willemse, Eline A. J.
AU - Scheltens, Philip
AU - van der Flier, Wiesje M.
AU - Teunissen, Charlotte E.
AU - ADNI
AU - Visser, Pieter Jelle
AU - Tijms, Betty M.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - CSF tau
KW - Gaussian mixture modelling
KW - Prognosis
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85098628419&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/33397464
U2 - 10.1186/s13195-020-00713-3
DO - 10.1186/s13195-020-00713-3
M3 - Article
C2 - 33397464
AN - SCOPUS:85098628419
VL - 13
JO - Alzheimer's Research & Therapy
JF - Alzheimer's Research & Therapy
SN - 1758-9193
IS - 1
M1 - 2
ER -