An Inflammatory View of Early Alzheimer’s Disease
Posted on by Lawrence Tabak, D.D.S., Ph.D.
Detecting the earliest signs of Alzheimer’s disease (AD) in middle-aged people and tracking its progression over time in research studies continue to be challenging. But it is easier to do in shorter-lived mammalian models of AD, especially when paired with cutting-edge imaging tools that look across different regions of the brain. These tools can help basic researchers detect telltale early changes that might point the way to better prevention or treatment strategies in humans.
That’s the case in this technicolor snapshot showing early patterns of inflammation in the brain of a relatively young mouse bred to develop a condition similar to AD. You can see abnormally high levels of inflammation throughout the front part of the brain (orange, green) as well as in its middle part—the septum that divides the brain’s two sides. This level of inflammation suggests that the brain has been injured.
What’s striking is that no inflammation is detectable in parts of the brain rich in cholinergic neurons (pink), a distinct type of nerve cell that helps to control memory, movement, and attention. Though these neurons still remain healthy, researchers would like to know if the inflammation also will destroy them as AD progresses.
This colorful image comes from medical student Sakar Budhathoki, who earlier worked in the NIH labs of Lorna Role and David Talmage, National Institute of Neurological Disorders and Stroke (NINDS). Budhathoki, teaming with postdoctoral scientist Mala Ananth, used a specially designed wide-field scanner that sweeps across brain tissue to light up fluorescent markers and capture the image. It’s one of the scanning approaches pioneered in the Role and Talmage labs [1,2].
The two NIH labs are exploring possible links between abnormal inflammation and damage to the brain’s cholinergic signaling system. In fact, medications that target cholinergic function remain the first line of treatment for people with AD and other dementias. And yet, researchers still haven’t adequately determined when, why, and how the loss of these cholinergic neurons relates to AD.
It’s a rich area of basic research that offers hope for greater understanding of AD in the future. It’s also the source of some fascinating images like this one, which was part of the 2022 Show Us Your BRAIN! Photo and Video Contest, supported by NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative.
 NeuRegenerate: A framework for visualizing neurodegeneration. Boorboor S, Mathew S, Ananth M, Talmage D, Role LW, Kaufman AE. IEEE Trans Vis Comput Graph. 2021;Nov 10;PP.
 NeuroConstruct: 3D reconstruction and visualization of neurites in optical microscopy brain images. Ghahremani P, Boorboor S, Mirhosseini P, Gudisagar C, Ananth M, Talmage D, Role LW, Kaufman AE. IEEE Trans Vis Comput Graph. 2022 Dec;28(12):4951-4965.
Alzheimer’s Disease & Related Dementias (National Institute on Aging/NIH)
Role Lab (National Institute of Neurological Disorders and Stroke/NIH)
Talmage Lab (NINDS)
The Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)
Show Us Your BRAINs! Photo and Video Contest (BRAIN Initiative)
NIH Support: National Institute of Neurological Disorders and Stroke