Core candidate neurochemical and imaging biomarkers of Alzheimer's disease⁎

A number of neuroimaging candidate markers are promising, such as hippocampus and entorhinal cortex volumes, basal forebrain nuclei, cortical thickness, deformation-based and voxel-based morphometry, structural and effective connectivity by using diffusion tensor imaging, tractography, and functional magnetic resonance imaging. CSF Aβ42, BACE1, total tau, and p-tau are substantially altered in MCI and clinical AD. Other interesting novel marker candidates derived from blood are being currently proposed (phase I). Biomarker discovery through proteomic approaches requires further research. Large-scale international controlled multicenter trials (such as the U.S., European, Australian, and Japanese Alzheimer's Disease Neuroimaging Initiative and the German Dementia Network) are engaged in phase III development of the core feasible imaging and CSF biomarker candidates in AD. Biomarkers are in the process of implementation as primary outcome variables into regulatory guideline documents regarding study design and approval for compounds claiming disease modification.