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An Inflammatory View of Early Alzheimer’s Disease

Posted on by Lawrence Tabak, D.D.S., Ph.D.

multicolored section of brain
Credit: Sakar Budhathoki, Mala Ananth, Lorna Role, David Talmage, National Institute of Neurological Diseases and Stroke, NIH

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.


[1] 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.

[2] 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


  • Barbara A Body says:

    Why was Budhathoki not a coauthor on the 2 papers cited?

  • Kassandra says:

    Has anyone studied whether cell surface receptor uptake of heavy metals and other chemicals are higher in cholinergic neurons? There is also the whole aspect of how the blood brain barrier can be breached in a multitude of fashion not just limited to blunt force trauma (or in conjunction with).

  • L Marcus says:

    nice picture, but if you want to find out how the disorder progresses you need people, not mice and photos of the brain will not tell you about how the brain changes over time in response to this disorder. You need a real time series (ask people in finance) of complete genome sequences in those who have the disorder to compare to their first degree relatives who have no obvious signs of the disorder. This could be followed up by targeted MRI scans of both also over time. You want to know what genetic and epigenetic changes occur over time to give you clues about the beginning and the progression of this disorder. Patients and relatives at risk and the data you collect have to be selected carefully. This has to be done not just with biologists but with people outside of this process.. that would mean the people best suited to predicting future events.. those on wallstreet ie Quants. As none of this is done as far as I know we will continue to be in the dark about all of this. Concentrating on amyloid plaques at the end will get you nowhere as do studies of mice. What you guys do has been done 100 times over and we are where we are.. time to change direction and approach. yes doing this the right way is expensive, difficult and complicated.. just like Alzheimers itself! what did you expect?

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