When applied to the AD population, these limitations are further worsened by other factors, such as the lack of well-defined diagnostic criteria, as AD patients are mostly identified based on probable diagnoses in the absence of appropriate disease biomarkers (e.g. positron emission tomography-derived amyloidosis and tau maps [95], lumbar puncture) and the even greater scalp-to-cortex distance due to the widespread cortical atrophy [96]. This evidence concerns the gene MAPT and Alzheimer disease.