Alzheimer's disease (AD) presents in early- and late-onset forms that share the same neuronal pathology but have different genetic causes. A new study by Qiang Liu, Guojun Bu (Washington University, St. Louis, MO), and colleagues now suggests that both AD forms are linked to a cholesterol pathway.
Cholesterol was already linked to late-onset AD. The best-known risk factor for this disease is a specific form of apolipoprotein E (apoE), which delivers lipids such as cholesterol to neurons. But early-onset AD stems from mutations in genes encoding amyloid precursor protein (APP) or its cleaving enzymes, which result in the accumulation of disease-associated Aβ amyloids. How these disparate pathways both lead to AD was not known.
In addition to Aβ, APP cleavage also produces the APP intracellular domain (AICD) peptide. Liu et al. now show that AICD blocks the apoE pathway, thereby lowering cholesterol levels in the...
