Magda Tsolaki
Alzheimer’s Disease (AD) is defined by the positivity of biomarkers of both amyloidopathy (A1) and tauopathy (T1) in line with the pathologic definition of the disease. The validity of measures is even more essential in preclinical stages, that is, in conditions where there are no other relevant signs helpful for diagnosing the disease. The quality of the measures should be unquestionable. Three phases of the disease can be distinguished in the continuum: The term of Asymptomatic at Risk for clinical AD (AR-AD) when the evolution to a clinical AD is less likely or still needs to be determined (only one pathophysiological marker considered abnormal). Asymptomatic at risk of AD consists of cognitively normal individuals for whom the biomarker pattern is insufficient to reach the above definition of AD. They can be characterized by the positivity of the pathophysiological biomarker (i.e. either “Asymptomatic A1” or “Asymptomatic T1”). The term of “preclinical AD” when the risk is particularly high (e.g., both Aß and Tau markers beyond pathologic thresholds). A clinical stage (“clinical AD”) defined by the occurrence of the clinical phenotype of AD (either typical or atypical) and which encompasses both the prodromal and the dementia stages. Topographical markers: Downstream topographical biomarkers (MRI and FDG-PET) are not suitable for defining preclinical AD. However, they may be useful for the screening of subjects at risk. New neuroimaging and magneto-encephalography (MEG)/electroencephalography (EEG) tools can target preclinical disease evolution through structural, metabolic, or functional measurements. To date, evidence from studies on blood-based biomarkers indicates a limited value for the characterization of preclinical stage of AD. However plasma protein biomarkers can be useful to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. In a recent study seven only from 34 proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ?4 non-carrier individuals only. If blood biomarkers can be used in clinical trials with asymptomatic to risk of AD patients then we can discuss about a hope to find a medication to stop the progression of asymptomatic to symptomatic AD.
