Moving away from amyloid beta to move on in Alzheimer research

Alzheimer's disease (AD) is characterized by a progressive decay of cognitive abilities, most remarkably (spatial) memory and learning. AD is diagnosed by clinical mental tests, often combined with the detection of neurobiological markers, mainly brain imaging studies and a decreased amyloid beta (Aß) level and/or increased total and hyper-phosphorylated Tau protein (tau-P) in cerebral spinal fluid (Hampel et al., 2008; Alzheimer's Association, 2014). The diagnosis is confirmed post-mortem by histopathological detection of senile plaques, composed of Aß accumulations, and tau-P-containing neurofibrillary tangles (Jellinger and Bancher, 1998). However, non-demented, aged patients may have a histopathology that is indistinguishable from AD (Price and Morris, 1999; Nelson et al., 2012). Furthermore, the brains of AD may have additional changes, such as (micro)vascular changes (Scheibel et al., 1989; de la Torre, 2002; Bell and Zlokovic, 2009; Hommet et al., 2011), white matter hyperintensities (Kandiah et al., 2015), and vacuolar cells, which are not considered as pathognomonic features under current standards (Nelson et al., 2012).