Selective affinity of extravasated brain-reactive IgG autoantibodies for pyramidal neurons is linked to brain amyloid beta deposition, neuronal dysfunction, and cognitive decline.

In AD pathogenesis, BBB compromise induces chronic extravasation of BrAbs and Aβ, an event that serves as a mechanistic link that initiates and perpetuates Aβ deposition in PNs. Deposition of Aβ may perturb PN function and lead to progressive cognitive decline.