Intracerebroventricular injection of amyloid-# peptides in normal mice to acutely induce alzheimer-like cognitive deficits

Abstract

Amyloid-# (A#) is a major pathological mediator of both familial and sporadic Alzheimer’s disease (AD). In the brains of AD patients, progressive accumulation of A# oligomers and plaques is observed. Such A# abnormalities are believed to block long-term potentiation, impair synaptic function, and induce cognitive deficits. Clinical and experimental evidences have revealed that the acute increase of A# levels in the brain allows development of Alzheimerlike phenotypes. Hence, a detailed protocol describing how to acutely generate an AD mouse model via the intracerebroventricular (ICV) injection of A# is necessary in many cases. In this protocol, the steps of the experiment with an A#-injected mouse are included, from the preparation of peptides to the testing of behavioral abnormalities. The process of preparing the tools and animal subjects before the injection, of injecting the A# into the mouse brain via ICV injection, and of assessing the degree of cognitive impairment are easily explained throughout the protocol, with an emphasis on tips for effective ICV injection of A#. By mimicking certain aspects of AD with a designated injection of A#, researchers can bypass the aging process and focus on the downstream pathology of A# abnormalities.