Authors: Shorena Janelidze, Niklas Mattsson, Ruben Smith, Erik Stomrud, Sebastian Palmqvist, Jeffrey L. Dage, Oskar Hansson
Published: 2020-12-07
DOI: 10.1002/alz.042489
Source: Full article
AbstractBackgroundThere is an urgent need for inexpensive and minimally invasive blood biomarkers of Alzheimer’s disease (AD) that could be used to detect early disease changes.MethodWe measured plasma levels of tau phosphorylated at threonine 217 (P‐tau217) in the prospective Swedish BioFINDER (BF) I and II studies (n=1057). BF‐II included cognitively unimpaired individuals (CU, n=275) and patients with mild cognitive impairment (MCI, n=161), AD dementia (n=114) and non‐AD neurodegenerative diseases (n=91) who underwent tau‐PET imaging using [18F]RO948. A subcohort of 157 participants had two or three tau‐PET scans on average 1.0 years apart (range 0.1‐1.6 years). In BF‐I, 264 CU and 152 MCI were followed longitudinally with clinical examinations to determine conversion to AD dementia (mean follow‐up 4.9 years, range 1.0‐8.6 years).ResultPlasma P‐tau217 levels were increased in CU individuals with abnormal amyloid‐β (Aβ)‐PET but still normal tau‐PET in the earliest Braak I‐II (entorhinal) ROI (Aβ‐PETpos/tau‐PETneg group vs Aβ‐PETneg/tau‐PETneg group, p<0.001). Furthermore, when testing the relation to global Aβ load in non‐linear spline models (Figure 1), we found that plasma P‐tau217 started to increase at Aβ‐PET SUVR of 0.39, which preceded the increase in tau‐PET measures (Aβ‐PET SUVR 0.42‐0.62). In line with these data, the majority of cases that were discordant for plasma P‐tau217 and tau‐PET in Braak I‐II were positive for P‐tau217 and negative for tau‐PET (P‐tau217pos/tau‐PETneg, n=68 [72%] and P‐tau217neg/tau‐PETpos, n=27 [ 28%]). Among participants with normal baseline tau‐PET, the rates of longitudinal increase in tau‐PET in the Braak I‐II ROI were higher in cases with abnormal plasma the P‐tau217 at baseline (p=0.017). Finally, in non‐demented individuals, abnormal levels of P‐tau217 were associated with increased risk of future AD dementia (hazard ratio 5.4; 95% confidence interval 3.5‐8.4; p<0.001).ConclusionPlasma P‐tau217 levels increase in early stages of AD when insoluble tau aggregates are not yet detectable by tau‐PET and predict both subsequent increase in tau‐PET as well as conversion to AD dementia. Plasma p‐tau217 holds promise as a marker for early AD‐pathology.