{Reference Type}: Journal Article
{Title}: β-amyloid monomer scavenging by an anticalin protein prevents neuronal hyperactivity in mouse models of Alzheimer's Disease.
{Author}: Zott B;Nästle L;Grienberger C;Unger F;Knauer MM;Wolf C;Keskin-Dargin A;Feuerbach A;Busche MA;Skerra A;Konnerth A;
{Journal}: Nat Commun
{Volume}: 15
{Issue}: 1
{Year}: 2024 Jul 10
{Factor}: 17.694
{DOI}: 10.1038/s41467-024-50153-y
{Abstract}: Hyperactivity mediated by synaptotoxic β-amyloid (Aβ) oligomers is one of the earliest forms of neuronal dysfunction in Alzheimer's disease. In the search for a preventive treatment strategy, we tested the effect of scavenging Aβ peptides before Aβ plaque formation. Using in vivo two-photon calcium imaging and SF-iGluSnFR-based glutamate imaging in hippocampal slices, we demonstrate that an Aβ binding anticalin protein (Aβ-anticalin) can suppress early neuronal hyperactivity and synaptic glutamate accumulation in the APP23xPS45 mouse model of β-amyloidosis. Our results suggest that the sole targeting of Aβ monomers is sufficient for the hyperactivity-suppressing effect of the Aβ-anticalin at early disease stages. Biochemical and neurophysiological analyses indicate that the Aβ-anticalin-dependent depletion of naturally secreted Aβ monomers interrupts their aggregation to neurotoxic oligomers and, thereby, reverses early neuronal and synaptic dysfunctions. Thus, our results suggest that Aβ monomer scavenging plays a key role in the repair of neuronal function at early stages of AD.