What’s New in Local Research

Bluewater Clinical Research Group, Dr. Anum Khalid

October 2022

Alzheimer’s disease (AD) is the most common form of dementia. It is a progressive brain disease that begins with mild memory loss and leads to deteriorating cognitive abilities with an eventual inability to carry our coherent conversations, respond appropriately to the environment and independently carry out activities of daily living. AD involves parts of the brain that control thought, memory and language. Despite being frequently seen in clinical practice, AD is poorly understood and to date, treatment options are limited.

New research carried out by a team of scientists in Japan has demonstrated how excess levels of tau – a key protein implicated in Alzheimer’s disease – impairs signalling between neurons in the brains of mice. More specifically, elevated levels of tau only decreased the transmission of high-frequency signals, while low-frequency transmission remained unchanged. High-frequency signals are typically involved in cognition and movement control. These results are very promising, providing a basis for the development of new treatments to alleviate AD symptoms and stop the progression of the disease.

Tau is produced in neurons, where it binds to and promotes the assembly of microtubules – long, thin filaments that maintain cell structure and provide pathways for transport within the cell. In AD, this normally soluble tau accumulates in high levels in certain brain regions and aggregates into insoluble structures called neurofibrillary tangles. Initially, research focus was placed on the visible neurofibrillary tangles being the hallmark of AD, but newer research emphasizes that it is the invisible levels of soluble tau that most closely correlate with cognitive decline.

The results of a new clinical trial in September 2022 revealed that a novel treatment, called Lecanemab, is the first of its kind to show a strong signal of cognitive benefit in a robust clinical trial. Lecanemab is a monoclonal antibody designed to clear clumps of amyloid protein from the brain that many believe is a root cause for Alzheimer’s disease. Lecanemab’s phase III clinical trial ran uninterrupted for a full 18 months and slowed decline to a statistically significant extent. While Lecanemab targets amyloid protein, this leaves tau protein accumulation to still be addressed. A multi-drug approach targeting both tau and amyloid would be most successful in treating a relentless neurodegenerative disease such as AD.