Project Overview

Among the earliest signs of preclinical Alzheimer’s disease (AD) are navigation impairments and the presence of abnormal Tau (aTau) proteins in the entorhinal cortex (EC), a brain region that represents space and movement. As AD progresses aTau spreads to the subiculum (Sub), a key region for memory encoding and retrieval. At present it is not known how navigation impairments in preclinical AD progress to the episodic memory loss seen in clinical AD. We hypothesize that the spread of EC aTau to Sub underlies the progress from navigation impairments to wider memory deficits. We will inject Cre-dependent mutant Tau into EC using a mouse line that limits Cre expression to the EC layer 3 to best approximate the aTau conditions of preclinical AD in humans. We will

1. assess the spread of aTau from the EC to Sub
2. determine if aTau disrupts spatial/mnemonic processing at the cellular and behavioural levels, and
3. attempt to rescue any impairments with circuit specific stimulation.

Principal Investigator

James Carmichael , Douglas Hospital Research Center

Partners and Donors

Alzheimer's Association