Comparing tau status determined via plasma pTau181, pTau231 and [18F]MK6240 tau-PET

• Background: Tau in Alzheimer's disease (AD) is assessed via cerebrospinal fluid (CSF) and Positron emission tomography (PET). Novel methods to detect phosphorylated tau (pTau) in blood have been recently developed. We aim to investigate agreement of tau status as determined by [18F]MK6240 tau-PET, plasma pTau181 and pTau231. Methods: We assessed cognitively unimpaired young, cognitively unimpaired, mild cognitive impairment and AD individuals with [18F]MK6240, plasma pTau181, pTau 231, [18F]AZD4694 amyloid-PET and MRI. A subset underwent CSF assessment. We conducted ROC curves to obtain cut-off values for plasma pTau epitopes. Individuals were categorized as positive or negative in all biomarkers. We then compared the distribution among concordant and discordant groups in relation to diagnosis, Aβ status, APOEε4 status, [18F]AZD4694 global SUVR, hippocampal volume and CSF pTau181. Findings: The threshold for positivity was 15.085 pg/mL for plasma pTau181 and 17.652 pg/mL for plasma pTau231. Most individuals had concordant statuses, however, 18% of plasma181/PET, 26% of plasma231/PET and 25% of the pTau231/pTau181 were discordant. Positivity to at least one biomarker was often accompanied by diagnosis of cognitive impairment, Aβ positivity, APOEε4 carriership, higher levels of [18F]AZD4694 global SUVR, hippocampal atrophy and CSF pTau181. Interpretation: Plasma pTau181, pTau231 and [18F]MK6240 seem to reflect different stages of tau progression. Plasma biomarkers can be useful in the context of diagnostic information and clinical trials, to evaluate the disease stage. Moreover, they seem to confidently evaluate tau-PET positivity. Funding: Moreover, this study was supported by Weston Brain Institute, Canadian Institute of Health Research and Fonds de Recherche du Québec. © 2022 The Authors

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Alzheimer's disease

Plasma

Positron emission tomography

Tau

amyloid beta protein

apolipoprotein E

apolipoprotein E4

biological marker

florquinitau f 18

phosphorylated tau 181

phosphorylated tau 231

tau protein

unclassified drug

adult

Alzheimer disease

amygdala

area under the curve

Article

biofluid analysis

blood sampling

brain size

cerebrospinal fluid

cerebrospinal fluid analysis

Clinical Dementia Rating

cohort analysis

comparative study

controlled study

diagnostic test accuracy study

education

female

hippocampus

human

human tissue

hypothalamus

major clinical study

male

mild cognitive impairment

Mini Mental State Examination

molecular evolution

nuclear magnetic resonance imaging

phenotype

prevalence

protein blood level

protein phosphorylation

receiver operating characteristic

risk assessment

sensitivity and specificity

standardized uptake value ratio

threshold limit value

white matter

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)