Tracking plasma biomarkers in cognitively unimpaired individuals at risk of Alzheimer’s disease

Abstract

AbstractAlzheimer’s disease (AD) is as a continuum that includes a preclinical phase, where individuals are cognitively unimpaired but there is evidence of amyloid‐β (Aβ) and tau pathology, followed by a clinical phase (including mild cognitive impairment and dementia). This preclinical phase is not a uniform or unvarying phase, but it is a long process during which Aβ and tau gradually accumulates until overt Aβ plaque deposition and neurofibrillary tangles are present. Moreover, this is a heterogeneous phase, there are differences in the rate of progression of those individuals that are Aβ‐positive to cognitive impairment and some of them will not even develop symptoms. It is important to develop biomarkers that accurately detect Preclinical AD, but also biomarkers to stage the disease, and prognostic biomarkers that identify those individuals that will progress to cognitive impairment. Furthermore, amid the new developments of disease modifying treatments, there is an unmet need to develop biomarkers to predict and monitor the response to an intervention.We now have a range of plasma biomarkers that detect symptomatic AD but also increase in Preclinical AD, including several epitopes of p‐tau (pT181, pT217, pT231), Aβ42/40, GFAP and NfL. Yet, there are differences between them. They may differ on which point of the long preclinical stage they start to increase, their discrimination accuracy, their longitudinal changes across the disease continuum or the physiopathological mechanism that they indicate. Moreover, the performance of plasma biomarkers may be influenced by sex and gender, race and ethnicity, or comorbidities. Therefore, the choice of the plasma biomarker may differ depending on its goal.In this presentation, plasma biomarkers in Preclinical AD will be reviewed and their differential roles will be discussed.