Advancing Important Research on Alzheimer’s Disease
Alzheimer’s disease (AD) is a neurodegenerative disorder most common among older adults. Bruce T. Lamb, PhD, is a researcher working to unravel the causes of AD.
Published August 22, 2018
By Bruce T. Lamb, PhD
Academy Contributor
What inspired you to research AD?
Initially, I worked at a lab focused on Down syndrome. One of the characteristics associated with the condition is an increased risk for AD. I was fascinated as to the why, so my career started trying to understand genes, like the amyloid precursor protein gene.
Since then, I’ve become more interested in the impact that AD has on society and how prevalent the disease will be in the coming decades. As part of this, I have been a strong advocate for increased funding for Alzheimer’s disease research, including organizing a cross-country bicycle ride called the Alzheimer’s Breakthrough Ride that helped lead to the passage of the National Alzheimer’s Project Act. Much more recently, it’s become personal. I have an in-law and parent, who have mild cognitive issues related to AD.
Why are your recent findings regarding the protein TREM2* so significant?
One of the important discoveries we’ve published, about TREM2 focused therapies, is that TREM2 has both age-related and pathology-related roles in disease mechanisms. For example, we found that TREM2 plays a detrimental role early and a protective role later in terms of development of Alzheimer’s disease pathologies. That’s important because it suggests that TREM2 may have a protective role at one stage and a detrimental role at another stage later, which relates to an acute versus chronic condition.
If we want to develop TREM2-focused therapies, we need to understand what stage of AD we are targeting and how to target it. This means that we will need to carefully identify the disease stage of AD patients for immune-focused therapies.
*TREM2 is found on the brain’s immune cells.
What is the MODEL-AD consortium and how does it help further the development of AD treatments?
The major goal of the consortium is to develop animal models. A 2015 NIH sponsored research meeting on AD identified the lack of accurate animal models as one roadblock in the development of potential treatments. Animal models allow us to study the development and progression of diseases and to test new treatments before they are given to people. It was appreciated that while we had a lot of decent models for early-onset AD, we didn’t have a lot of good models to decipher the more common late-onset AD.
During the initial five year funding period we hope to generate up to 50 new models and release the animals and data to the wider community as quickly as possible. The goal is to make the models available for use in understanding AD mechanisms and for testing candidate therapeutics.
Is it more realistic for a researcher to look into disease modifying therapies rather than a cure?
We’d love to find a cure. But if you look at the demographics of AD, researchers could make a huge impact by delaying its onset. If you delay the onset by five years, incidence would be reduced by half, which would have huge implications for public health. My research is concerned with trying to understand AD mechanisms and then develop therapies targeting these mechanisms.
While there is still some hope for anti-amyloid therapies and anti-tau therapies, we need to identify the next target while clinical trials for those therapies move forward. This is where immune pathways come in as there’s abundant evidence from genetics and systems biology that these are promising pathways for late onset AD.
What will the next decade bring in the treatment of AD?
We’re headed to more precision medicine type approaches. That means we will identify patients based on either genetics or bio-markers to identify a unique population and deliver therapies specified for their biomarkers. This is already happening with some of the anti-amyloid therapies, and patients are being selected based on amyloid PET scans, or CSF measures.
Also read: Predicting the Onset of Alzheimer’s Disease
