Alzheimer’s Disease: Physiological and Pathogenetic Role of the Amyloid Precursor Protein (APP), its Aβ-Amyloid Domain and Free Aβ-Amyloid Peptide

To understand synaptic loss and neurodegeneration in Alzheimer’s disease, we have tried to consider the physiological functions of the amyloid precursor protein (APP), its Aβ-amyloid domain and of free Aβ peptide. The latter is a normal metabolic product of APP and the principal subunit of the amyloid plaques that are characteristic of Alzheimer’s disease. From studies in transgenic Drosophila melanogaster and primary mammalian neurons, we suggest that, in neurons, APP exhibits as a physiological function the negative regulation of synaptic strength whereas in nonneuronal cells APP appears to regulate cell-cell and cell-matrix adhesion.