Just as cholesterol and lipid rafts have been shown to affect APP processing, APP-derived species have been shown to impact on cholesterol and lipid homeostasis. Aβ peptides modulate the metabolism of cholesterol, in particular its esterification rate, and of phospholipids in hepatocytes, neuronal cells, and in the entire brain Koudinova et al., 1996 Koudinova et al., , 2000 . It was also found that Aβ peptides alter vesicle trafficking and cholesterol homeostasis (Liu et al., 1998) . On the other hand, it was shown that cholesterol binds to APP at the α-secretase cleavage sites and Aβ itself can bind cholesterol and prevent its interaction with low-density lipoprotein (Yao and Papadopoulos, 2002) . This confirmed that Aβ might act as a component of lipoprotein complexes and affect reverse cholesterol transport from neuronal tissue to the periphery in addition to its role in cholesterol synthesis and intracellular dynamics (Koudinov et al., 2001; Michikawa et al., 2001) . In a later study Aβ 40 has been shown to inhibit a key enzyme in the biosynthesis of cholesterol, HMG CoA reductase (Grimm et al., 2005) . Further to this, APP intracellular domain AICD was found to regulate cholesterol levels via LRP1 (Grosgen et al., 2010) . However, there also are data reporting that cholesterol in physiological concentrations can protect neuronal cells Frontiers in Physiology | Membrane Physiology and Biophysics against Aβ-induced toxicity and slow down the process of formation of toxic aggregates of Aβ with metal ions, in particular with aluminum (Granzotto et al., 2011) . This correlates with the data suggesting that cholesterol may have a protective effect against membrane disruption by amyloid species (in this case, Aβ-derived diffusible ligands: ADDLs). Cholesterol supplemented SH-SY5Y cells were shown to display reduced binding of ADDLs to the plasma membrane, while oligomers increased in membrane presence after treatment with the cholesterol-depleting agent MβCD (Cecchi et al., 2009) .