The amyloid precursor protein known for its role in causing familial Alzheimer's disease directly interacts with secreted proteins, called Wnts, known for their key roles in brain development and homeostasis, suggesting the two processes may be directly linked.
Biochemical studies in combination with computational modeling and molecular dynamics simulations reveal that the lipid bilayer promotes intramembrane proteolysis by stabilizing the enzyme-substrate complex and the protease active site.
Diane M Bushman, Gwendolyn E Kaeser ... Jerold Chun
Somatically derived genomic mosaicism in the form of increased DNA content and APP copy number in single neurons plausibly has a function in sporadic Alzheimer’s disease and points to functions for single-neuron gene copy number changes.
β-CTF of APP, not Aβ, induces synaptic loss in a cell-autonomous manner, revealing APP misregulation may contribute to the pathogenesis of Alzheimer's disease via an Aβ-independent mechanism.
Proteins implicated in Alzheimer’s disease, including amyloid precursor protein and ApoE receptors, interact with each other and with a signalling molecule called agrin to influence the development of the neuromuscular junction.
Peer-Hendrik Kuhn, Alessio Vittorio Colombo ... Stefan F Lichtenthaler
The metalloprotease ADAM10 modulates axon and synapse function by cleaving numerous synaptic and axonal membrane proteins in the central nervous system.
Molecular genetics identifies a novel microglial pathway essential for mouse brain development and a previously unknown anti-inflammatory activity of monomeric amyloid β that activates this pathway.
Tomas Fanutza, Dolores Del Prete ... Luciano D’Adamio
A naturally occurring intracellular peptide, derived by processing the Alzheimer's protein APP, reduces synaptic transmission by acting as a dominant negative of APP.
Reducing Akt-mediated huntingtin phosphorylation decreases APP accumulation at the synapse by reducing its anterograde axonal transport and ameliorates learning and memory in a mouse model of familial Alzheimer disease.
The APP intracellular domain (AICD) physiologically regulates synaptic GluN2B-containing NMDA receptor current, a process that could contribute to pathological Alzheimer's disease-related synaptic failure upon increase of AICD levels in adult neurons.
