MAPT and Alzheimer disease: Mechanistically, we demonstrated in such rabbits that elevated levels of plasma cholesterol disrupted blood–brain barrier integrity (Ghribi, 2006; Chen et al., 2008a), increased brain levels and the neuronal endolysosome accumulation of apoB (the exclusive apolipoprotein of LDL cholesterol that is normally found only in the periphery), disturbed the structure and function of neuronal endolysosomes, and led to the appearance of pathological features of AD including disrupted synaptic integrity, brain deposition of Aβ, and tau pathology (Chen et al., 2010).