Locus Coeruleus in the Pathogenesis and Prevention of Alzheimer’s Disease

Locus Coeruleus in the Pathogenesis and Prevention of Alzheimer’s Disease

Dr. Qi Yuan
Professor of Neuroscience
Faculty of Medicine

Monday, March 28, 2022
Time: 1-2 pm
Location: Arts Building Room 1046 (IN PERSON)

Abstract

The brainstem locus coeruleus (LC), the main source of brain norepinephrine, is critically involved in several functions including wakefulness, vigilance, attention, learning and memory. LC functioning is firing pattern-dependent. Phasic pattern promotes novelty and learning, while high tonic activity associates with stress and anxiety. LC has been identified as a key structure in Alzheimer’s disease (AD) development. Braak and colleagues propose that soluble abnormally phosphorylated tau (pre-tangle tau) originates in the LC early in life.  The spreading of pre-tangle tau to other neuromodulatory areas and transentorhinal cortex constitutes Braak’s pre-tangle AD stages. Pre-tangle stages appear to be universal in human, however, only a portion of us develop AD. The selective vulnerability of individuals for AD is not understood. In this talk, I will discuss our established LC pre-tangle tau model in rats which mimics the origin of hyperphosphorylated tau in human. Our results show that LC pre-tangle tau progression generates both preclinical AD pathological changes and cognitive decline in the absence of amyloid. The odor discrimination deficits are similar to human odor deficits seen with aging and preclinical AD. More recently, we have shown that differential LC activity patterns influence the pre-tangle tau pathophysiology. These results argue that variations in environmental experiences associated with differing LC activity patterns may account for individual susceptibility to development of AD in humans.

For short bio, you can reference to my MUN website.

Faculty of Medicine - Faculty of Medicine, Memorial University of Newfoundland (mun.ca)