Membrane Orientation of the Alzheimer’s Disease–Associated Presenilins

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is clinically characterized by a progressive dementia. All brains of patients with AD display cerebral amyloid plaques, which are extracellular deposits mainly consisting of the 40-and 42/43-residue β-amyloid peptide (βA); intraneuronal neurofibrillary tangles consisting of hyperphosphorylated tau; and extensive neuronal loss. In the large majority of cases, AD occurs sporadically with an age of onset of more than 65 years. Nonetheless, there are a number of families in which the disease has an early age of onset and a clear autosomal dominant inheritance pattern.