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Shannon Macauley @macauleylab.bsky.social · 01/05/2026

And critically: 🔥 Selective depletion of disease-associated microglia → ↓ Clec7a⁺ → ↓ CD68⁺ → ↓ peri-plaque microglia

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Shannon Macauley @macauleylab.bsky.social · 01/05/2026

Importantly!!! We can block LDH and: ✔ ↓ brain lactate (~60%) ✔ ↓ ISF Aβ (~50%)

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Shannon Macauley @macauleylab.bsky.social · 01/05/2026

This isn’t just correlation. We show: 👉 Inflammation (LPS) → ↑ lactate + ↑ reactive microglia 👉 Lactate itself alters Aβ aggregation dynamics Lactate is functionally active, not passive.

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Shannon Macauley @macauleylab.bsky.social · 01/05/2026

A lot of LDHA is extracellular, but the microglia surrounding plaques are highly glycolytic (LDHA+)

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Shannon Macauley @macauleylab.bsky.social · 01/05/2026

Around plaques, we see: 🔥 LDHA enrichment 🔥 Reactive (Clec7a⁺, CD68⁺) microglia 🔥 A highly glycolytic microenvironment → A localized immunometabolic niche

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Shannon Macauley @macauleylab.bsky.social · 01/05/2026

But where is this lactate coming from? Not astrocytes. Using publicly available datasets in the human AD brain, we show: 👉 Microglia are the highest LDHA-expressing cells (lactate producers) 👉 Especially a glycolytic, cytokine-producing subtype (MG7) of microglia that are found early in AD

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Shannon Macauley @macauleylab.bsky.social · 01/05/2026

This reflects a shift toward glycolysis and away from oxidative metabolism and neurotransmitter synthesis in APP/PS1 mice.

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Shannon Macauley @macauleylab.bsky.social · 01/05/2026

We found that brain lactate increases early with amyloid plaques, not aging. Consistent with what we found in 2016 with Robert Cumming's group: www.jneurosci.org/content/36/6...

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Shannon Macauley @macauleylab.bsky.social · 17/04/2026

Accepted! Can’t wait to share this work! Way to go, @clairashley.bsky.social !

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Shannon Macauley @macauleylab.bsky.social · 17/03/2026

At #ADPD2026? Stop by and see work from the lab! @rileyirmen.bsky.social's talk tomorrow on tau, metabolism, and sleep. @clairashley.bsky.social 's work on metabolic reprogramming in microglia in AD. @Sierra Turner's work on KATP channel inhibition to reduce tau pathology & reactive glia!

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Shannon Macauley @macauleylab.bsky.social · 23/01/2026

We used quantitative EEG analysis to assess changes in sleep macro and micro-architecture. We found tau pathology disrupts NREM and REM sleep, specific to the light period, but compromising beta activity which normally reflects cortical synchrony and GABA activity.

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Shannon Macauley @macauleylab.bsky.social · 23/01/2026

EEG recordings confirmed this state of hyperexcitability and lack of coordination among brain networks, while wide field optical imaging showed exaggerated responses of excitatory neurons to sensory stimulation, despite less glutamatergic neurons, confirming hyperexcitability in the system.

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Shannon Macauley @macauleylab.bsky.social · 23/01/2026

By tracing how glucose is used in the brain, we discovered that tau redirects glucose toward making glutamate and not ATP. This increased excitatory activity, reduced inhibition. This creates E/I imbalance that favors overexcitation, even though brain's mitochondria remains intact.

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Shannon Macauley @macauleylab.bsky.social · 23/01/2026

In this study, we show that tau pathology rewires how the brain uses energy, causes hyperexcitability, network desynchrony, and sleep loss. In mice, we found that tau surprisingly preserves normal body-wide metabolism and daily fluctuations in metabolic rhythms typically lost with aging.

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Shannon Macauley @macauleylab.bsky.social · 14/12/2025

#ArtAdventCalendar, Day 14! Another hometown fav. Watercolor, Lobster Landing, Clinton, CT

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Shannon Macauley @macauleylab.bsky.social · 12/12/2025

#ArtAdventCalendar, Day 11! Watercolor, Seashells, Hammonasset State Park, Madison, CT.

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Shannon Macauley @macauleylab.bsky.social · 11/12/2025

#ArtAdventCalendar, Day 11 Watercolor, seagull on channel marker, Clinton Harbor, Clinton CT

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Shannon Macauley @macauleylab.bsky.social · 10/12/2025

#ArtAdventCalendar, Day 10 Watercolor, alcohol inks, acrylics. Inspired by Ramon y Cajal and Greg Dunn’s work.

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Shannon Macauley @macauleylab.bsky.social · 07/12/2025

I forgot about this! #ArtAdventCalendar Day 7 Watercolor, mouse, EVs. Painted it for my student after we discovered a method to isolate EVs from the interstitial fluid of the mouse’s brain (Pait et al, 2023).

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Shannon Macauley @macauleylab.bsky.social · 05/12/2025

So very pretty! Iba1, Cmec7a, Amylo-glo. Courtesy of @clairashley.bsky.social

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Shannon Macauley @macauleylab.bsky.social · 24/11/2025

We're very excited for our upcoming CNS Metabolism Symposium at University of Kentucky! We have a great line up of speakers, including our ATP Showcase and a keynote from Dr. Tim Ryan! Register now! uky.az1.qualtrics.com/jfe/form/SV_...

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Shannon Macauley @macauleylab.bsky.social · 18/11/2025

At SFN? Check out Dr. Karina Meyer-Acosta’s talk on APOE, neurodevelopment, and network formation using organoids. We were lucky to have Kaisha join the lab earlier this fall from Dr. Jenny Hsieh’s lab for her postdoc!

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Shannon Macauley @macauleylab.bsky.social · 17/11/2025

At #SFN2025? Stop by @ncons95.bsky.social and Sierra’s posters to learn about research from the lab!

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Shannon Macauley @macauleylab.bsky.social · 31/10/2025

Macauley Lab- dressed to impress- at the Markesbery Symposium! @uksbcoa.bsky.social

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Shannon Macauley @macauleylab.bsky.social · 11/10/2025

Pretty Fluorescent Friday by Sierra Turner!

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Shannon Macauley @macauleylab.bsky.social · 05/10/2025

Macauley Lab representing at the Walk to End Alzheimer’s!

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Shannon Macauley @macauleylab.bsky.social · 12/09/2025

Confocal bat signal! Or Ant-man maybe? Guess that makes Clair our lab’s super hero!!!

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Shannon Macauley @macauleylab.bsky.social · 10/09/2025

Absolutely fantastic talk and visit with @mzilberter.bsky.social ! Thanks so much for coming to visit us in Kentucky and sharing your elegant work, Misha!

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Shannon Macauley @macauleylab.bsky.social · 22/08/2025

I’m absolutely elated to hear our UK Prep R25 received its NOA for this year! So glad our lab’s very own, Sierra Turner, can continue on in this program!!!

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Shannon Macauley @macauleylab.bsky.social · 16/08/2025

What a day for the lab! Clair Ashley CRUSHED her quals and is officially a PhD candidate! Amunet Jacobs, MD/PhD student, got her white coat and is officially part of the lab! Nick Constantino got not one but two awards!! 1) Poster award at CASH-KY Symposium & 2) SFN Trainee Development Award!

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Shannon Macauley @macauleylab.bsky.social · 14/08/2025

Macauley Lab 2025! What a fantastic group to work with! 🧠 🔬

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Shannon Macauley @macauleylab.bsky.social · 07/07/2025

My attempts to paint more- small watercolors of 1) Owl seen in Whistler at recent Keystone conference & 2) Gull (or sandpiper maybe?) from trip to CT to visit family. Diggin my painted memories... I seem to be in a bird phase…

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Shannon Macauley @macauleylab.bsky.social · 01/06/2025

Needed to escape into art. Watercolor doodle of a Carolina Chickadee/Black Capped Chickadee. Couldn’t really tell which was dining at our bird feeders.

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Shannon Macauley @macauleylab.bsky.social · 21/05/2025

Relieved, grateful, and most of excited to continue exploring how metabolic reprogramming contributes to Alzheimer’s disease progression. Thankful for our CART grant and recent NOA from the NIA to support this work.

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Shannon Macauley @macauleylab.bsky.social · 21/05/2025

As always, a wonderful visit and engaging discussion with @erinmgibson.bsky.social !! Fabulous researcher, stellar mentor, and superb colleague.

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Shannon Macauley @macauleylab.bsky.social · 18/05/2025

What an amazing week! Big thank you to my long time collaborator & friend, Adam Bauer, and his lab, Xiaodan Wang and Kaelyn Schloss, for coming to UK and upgrading our widefield optical imaging system. We have maps! And stim! Sci BFFs are the BEST collabs!

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Shannon Macauley @macauleylab.bsky.social · 16/05/2025

I cannot wait for @erinmgibson.bsky.social visit to Univeristy of Kentucky next week!!!! How lucky are we!!! 🤩🤩🤩

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Shannon Macauley @macauleylab.bsky.social · 10/05/2025

My 12yo: Did you mean to put DNA curls in M’s hair? 🧬 💃

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Shannon Macauley @macauleylab.bsky.social · 08/05/2025

Sciart doodle. Inspired by Ramon y Cajal & Greg Dunn.

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Shannon Macauley @macauleylab.bsky.social · 25/04/2025

At #Tau2025? Go see @rileyirmen.bsky.social ‘s poster on tau, GABA, and sleep! Many thanks to Emmanuel Planel for the fabulous selfie from the morning session.

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Shannon Macauley @macauleylab.bsky.social · 11/04/2025

2025 CCAD Reunion Conference has come to an end in beautiful Puerto Rico! I’ve been a part of the Charleston Conference on Alzheimer’s Disease and New Vision Research for a decade now. Its positive impact on my career and others is indescribable. Til next time!

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Shannon Macauley @macauleylab.bsky.social · 03/04/2025

Such a wonderful time at University of Michigan giving Neurology Grand Rounds. Thanks to Hank Paulson and Catherine Kaczorowski for the invitation!

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Shannon Macauley @macauleylab.bsky.social · 23/03/2025

Amid a challenging political climate, I'm torn on conference travel. But after returning from #APOE2025, nothing beats being fully immersed in science, seeing trainees shine, sparking new collaborations, & connecting with researchers I've long admired in person. So worth it.

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Shannon Macauley @macauleylab.bsky.social · 21/03/2025

Macauley Lab needed a win today! Thank you to UK Women’s Basketball for providing it. What a great first round win!!! And there was ice cream. Yum! @ncons95.bsky.social @rileyirmen.bsky.social

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Shannon Macauley @macauleylab.bsky.social · 09/03/2025

Happy Int’l Women’s Day! I’d be remiss if I didn’t acknowledge the amazing women in my lab that make me so proud. I’m optimistic about our future because of these ladies’ grit, talent, and smarts!

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Shannon Macauley @macauleylab.bsky.social · 14/02/2025

Seems like we could all use some more love. Happy Valentine’s Day in several nerdy, science themed valentines. Nothing says love like a dissected nematode, an anatomically correct gummy heart, and a stereotax.

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Shannon Macauley @macauleylab.bsky.social · 14/02/2025

Seeing lots of vaccine schedules posted and reposted, which is great! Most are for children under 7yo. Children and teens need vaccines, too. Like HPV, which can 100% protect women from cervical cancer.

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Shannon Macauley @macauleylab.bsky.social · 31/01/2025

Lots of post on various groups about self care during these challenging times. While I find myself lifting heavier and harder than normal, my hubby is rage smoking bacon. Is this what they mean by work/life balance?

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