The Interplay Between Beta-Amyloid 1–42 (Aβ1–42)-Induced Hippocampal Inflammatory Response, p-tau, Vascular Pathology, and Their Synergistic Contributions to Neuronal Death and Behavioral Deficits
Beatriz Calvo‐Flores Guzmán, Tessa Elizabeth Chaffey, Thulani H. Palpagama, Sarah L. Waters, Jordi Boix, Warren P. Tate, Katie Peppercorn, Michael Dragunow, Henry J. Waldvogel, Richard Lewis Maxwell Faull, Andrea Kwakowsky
Abstract
Alzheimer's disease (AD), the most common chronic neurodegenerative disorder, has complex neuropathology. The principal neuropathological hallmarks of the disease are the deposition of extracellular -amyloid (A) plaques and neurofibrillary tangles (NFTs) comprised of hyperphosphorylated tau (p-tau) protein. These changes occur with neuroinflammation, a compromised blood-brain barrier (BBB) integrity, and neuronal synaptic dysfunction, all of which ultimately lead to neuronal cell loss and cognitive deficits in AD. A 1-42 was stereotaxically administered bilaterally into the CA1 region of the hippocampi of 18-month-old male C57BL/6 mice. This study aimed to characterize, utilizing immunohistochemistry and behavioral testing, the spatial and temporal effects of A 1-42 on a broad set of parameters characteristic of AD: p-tau, neuroinflammation, vascular pathology, pyramidal cell survival, and behavior. Three days after A 1-42 injection and