Abstract
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.
Original language | English |
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Article number | 2 |
Number of pages | 25 |
Journal | Alzheimer's Research & Therapy |
Volume | 13 |
Issue number | 1 |
DOIs | |
Publication status | Published - 4 Jan 2021 |
Keywords
- accuracy
- alzheimer's disease
- cerebrospinal-fluid biomarker
- csf biomarkers
- csf tau
- decline
- dementia
- diagnosis
- gaussian mixture modelling
- markers
- national institute
- pathology
- prognosis
- signature
- Prognosis
- CEREBROSPINAL-FLUID BIOMARKER
- DEMENTIA
- MARKERS
- CSF BIOMARKERS
- PATHOLOGY
- SIGNATURE
- CSF tau
- NATIONAL INSTITUTE
- Alzheimer's disease
- DIAGNOSIS
- ACCURACY
- DECLINE
- Gaussian mixture modelling