Plasma P-tau217 predicts cognitive decline in preclinical Alzheimer’s disease
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The plasma biomarker P-tau217 predicted cognitive decline in patients with preclinical Alzheimer’s disease and may complement cerebrospinal fluid and positron emission tomography as a patient-screening tool in clinical trials.
“There is variability in the rates of cognitive decline in preclinical AD,” Niklas Mattsson-Carlgren, MD, PhD, of the Clinical Research Memory Unit at Lund University in Sweden, and colleagues wrote in JAMA Neurology. “Inclusion of individuals with low risk of decline reduces clinical trial power. Successful trials of preclinical AD would benefit from methods to enrich for individuals likely to experience cognitive decline.”
Carlgren and colleagues sought to assess various plasma biomarkers in predicting cognitive decline in beta-amyloid positive but cognitively unimpaired adults. The primary outcome of interest was longitudinal measures of cognition over a median of 6 years using the Mini-Mental State Examination (MMSE) and the modified Preclinical Alzheimer Cognitive Composite (mPACC).
Researchers collected data from two prospective cohort studies, the Swedish BioFINDER-1 and Wisconsin Registry for Alzheimer Prevention (WRAP), from 2010 to 2021 and included 564 participants with brain beta-amyloid pathology, defined by CSF beta-amyloid 42/40 in the BioFINDER-1 study and Pittsburgh Compound B PET in the WRAP study.
Other biomarkers assessed included baseline plasma P-tau181, P-tau217, P-tau231, glial fibrillary filament protein and neurofilament light.
Of 171 participants included in analyses, 119 were from the BioFINDER-1 study (mean age, 73 years; 60.5% women) and 52 were from the WRAP study (mean age, 64.4 years; 65.4% women).
According to study results, plasma P-tau217 was superior in predicting cognitive decline in the mPACC (model R2 = 0.41) and the MMSE (model R2 = 0.34) and bested the covariates-only models (R2 = 0.23 in mPACC and R2 = 0.04 in MMSE) in the BioFINDER-1 cohort.
Researchers also reported that plasma P-tau217 was associated with mPACC (R2 = 0.13 vs. 0.01 in the covariates-only model) and MMSE slopes (R2 = 0.29 vs. 0.24 in the covariates-only model) in the WRAP cohort, further validating results.
Moreover, sample size was significantly reduced by identifying beta-amyloid positive, cognitively unimpaired individuals with high plasma P-tau217 in hypothetical clinical trials.
“This type of enrichment may increase the power of clinical trials in the earliest stages of AD, when cognitive decline is variable and the power to detect associations in unenriched populations of beta-amyloid positive, [cognitively unimpaired] individuals is low,” researchers wrote.
“In this study, plasma P-tau217 predicted cognitive decline in patients with preclinical AD,” Mattsson-Carlgren and colleagues concluded. “These findings suggest that plasma P-tau217 may be used as a complement to CSF or PET for participant selection in clinical trials of novel disease-modifying treatments.”