Does the Little-Studied Big Tau Protect Against Alzheimer's Disease?

The main project aim is to assess whether a version of tau, known as big tau, is protective against Alzheimer’s disease.

Tau is a key protein in the development of Alzheimer’s disease, accumulating inside nerve cells and impeding their communication systems. But the brain makes several versions of tau, including a little-studied form, known as big tau. Dah-eun (Chloe) Chung, PhD, brings the focus to big tau in this project to address the question of whether big tau offers protection against Alzheimer’s.

As a first step, Dr. Chung and her colleagues will create new genetic animal models that do not make any big tau and determine how effectively tau buildup can be induced in the brain. In a separate set of studies, they will identify other proteins that interact with big tau and determine how they affect the functions and features of big tau. As part of this work, they will be using a novel antibody that specifically tags big tau.

For both project aims, the new research tools that Dr. Chung and her colleagues are developing can be used for other studies of big tau and other versions of tau. The findings also may highlight new therapeutic targets in Alzheimer’s disease.

While tau has been heavily studied for the past several decades as one of the key disease proteins in Alzheimer’s disease, an atypical “big tau” isoform has been under-explored especially from a therapeutic standpoint. My study is unique as it will revisit this less-known tau isoform to evaluate its potential therapeutic benefits in Alzheimer’s disease. Also, my study will showcase the application of innovative tools such as a new genetic mouse model that lacks big tau and an antibody that can specifically detect big tau.

We currently lack effective tau-targeting therapies for Alzheimer’s disease despite the strong correlation between the degree of tau pathology and cognitive decline in patients. As such, completion of my study will expand our knowledge of big tau biology, revealing the complex nature of tau protein and highlighting the importance of studying disease proteins in an isoform-dependent manner. Importantly, findings from this study may contribute to developing new therapeutic strategies to target abnormal aggregation of tau in Alzheimer’s disease and related dementia.