Mechanism of Alzheimer Amyloid β-Protein Precursor Localization to Membrane Lipid Rafts

Alzheimer’s disease (AD) is a group of common neurodegenerative diseases associated with progressive dementia with aging. The principal pathological hallmarks of AD are senile pla‐ ques and neurofibrillary tangles in the brain, which are found at significantly higher fre‐ quencies in AD patients than age-matched healthy (non-AD) subjects [1]. Senile plaques consist mainly of 39–43 amino-acid amyloid-β (Aβ) peptide, which is generated by sequen‐ tial proteolytic processing of amyloid β-protein precursor (APP) (Figure 1) [2]. Common Aβ species generated in the human and murine brain are Aβ40 and Aβ42. Mutations in APP and Presenilin, which have been identified as familial AD-causative genes, result in in‐ creased Aβ production and/or an increased ratio of neurotoxic Aβ42.