Sign in

Shannon Macauley

@macauleylab.bsky.social
2.8K followers 1K following 545 posts

Associate Prof, PhD, wife, mom. Alzheimer’s disease | metabolism | sleep| glia | I ❤️ lactate | macauleylab.com **views are mine, not my employer**

PostsRepliesMedia
Reposted by Shannon Macauley
UK Sanders-Brown Center on Aging @uksbcoa.bsky.social · 21/07/2026
Previously, scientists believed that sleep loss in Alzheimer’s was caused by dying neurons or the physical clutter of amyloid plaques. However, findings from the @macauleylab.bsky.social suggest the problem is a “whole house response” scenario. @ukresearch.bsky.social
uknow.uky.edu
Two hours of sleep restored: UK researchers make Alzheimer’s breakthrough
In a study published in the journal Alzheimer’s & Dementia, a team led by Shannon L. Macauley, Ph.D., an associate professor of physiology in the UK College of Medicine, and first author Nicholas ...
0104
Reposted by Shannon Macauley
Alzheimer's Association @alzassociation.bsky.social · 12/07/2026
🏆 Linda Jo Van Eldik, Ph.D. is the 2026 recipient of the Khalid Iqbal Lifetime Achievement Award In Alzheimer’s Disease Research.
171
Reposted by Shannon Macauley
UK Sanders-Brown Center on Aging @uksbcoa.bsky.social · 06/07/2026
Kudos to trainees in the @macauleylab.bsky.social who are representing Sanders-Brown well, sharing research abroad at the 𝐈𝐧𝐭𝐞𝐫𝐧𝐚𝐭𝐢𝐨𝐧𝐚𝐥 𝐂𝐨𝐧𝐟𝐞𝐫𝐞𝐧𝐜𝐞 𝐨𝐧 𝐁𝐫𝐚𝐢𝐧 𝐄𝐧𝐞𝐫𝐠𝐲 𝐌𝐞𝐭𝐚𝐛𝐨𝐥𝐢𝐬𝐦 in Spain. @ukresearch.bsky.social
Research trainee Clair Ashley shown at the podium presenting a slide showing reactive microglia link lactate metabolism and early Alzheimer's pathology.Research trainee Evan Neary shown at the podium presenting a slide showing a high-fat, high-sugar diet drives regional plaque deposition and vascular remodeling in a model of amyloid pathology.
021
Reposted by Shannon Macauley
I-75 Scientist @flscitriguy.bsky.social · 01/07/2026
Ok, it's getting to be about a month out from the next F3# due dates. Students, when contacting a program officer about fit, send a draft of your specific aims page. Yes, the whole page. Context of your project is important. The elevator pitch in an email is less helpful.
02218
Reposted by Shannon Macauley
LifeCanvas Technologies @lifecanvastech.bsky.social · 17/06/2026
How can the relationship between #Alzheimers pathology & sleep quality help us diagnose & treat the disease at earlier stages? Nicholas Constantino et al. used LifeCanvas whole 🧠 mapping to uncover a key role for microglia in amyloid-related sleep disruption: bit.ly/4vR6BPy @macauleylab.bsky.social
042
Reposted by Shannon Macauley
Andrew Hardaway @andrewhardaway.bsky.social · 03/06/2026
If you have not left a public comment on the draconian OMB-2026-0034, here's a quick thread to make it easy. #standupforscience #neuroskyence Click here: www.regulations.gov/document/OMB...
regulations.gov
Regulations.gov
55847
Shannon Macauley @macauleylab.bsky.social · 27/05/2026
Congratulations to @rileyirmen.bsky.social for being named a 2026 MVP Awardee through UK's College of Medicine!!! medicine.uky.edu/news/congrat...
medicine.uky.edu
Congratulations to our 2026 MVP Awardees
2026 MVP Awards, Mission Values Pillar Awards, UK College of Medicine, faculty, staff, and learner recognition
030
Reposted by Shannon Macauley
Hao Yin @haoyin.bsky.social · 24/05/2026
Organotypic Pericrine dictates Postnatal Tissue 🫁🧠Morphogenesis 🐭Pdgfrb+ mural cell BDNF/HGF KO ⏬Lung Angiogenesis Alveologenesis Not🧠BBB/astroglia Nodal KO ⏬Brain Angiogenesis ⏫Astrogliosis ⏫Microglia activ Not🫁 Outstanding!👏 @ralfhadams.bsky.social #NatComm 2026 www.nature.com/articles/s41...
052
Reposted by Shannon Macauley
Aaron Wilber @aaronwilber.bsky.social · 24/05/2026
The oscillatory biology of sleep: Linkage to dementia | Science www.science.org/doi/10.1126/...
science.org
The oscillatory biology of sleep: Linkage to dementia
During wakefulness, neuromodulators operate largely independently to support behavior and cognition. By contrast, sleep reorganizes their activity into a coordinated brain rhythm. During sleep, the ma...
0215
Shannon Macauley @macauleylab.bsky.social · 01/05/2026
Big congrats to Clair!!! And major thanks to our collaborators: @johnsonlab.bsky.social @karchlab.bsky.social @morganti.bsky.social
020
Shannon Macauley @macauleylab.bsky.social · 01/05/2026
This reframes lactate as: 🧠 A signaling metabolite 🧠 A regulator of microglial state 🧠 A therapeutic target
130
Shannon Macauley @macauleylab.bsky.social · 01/05/2026
Conceptually: Amyloid → microglial glycolysis → lactate ↑ → sustains inflammation + alters Aβ dynamics Interrupt lactate → ❌ immunometabolic microglia ❌ Aβ signaling axis
120
Shannon Macauley @macauleylab.bsky.social · 01/05/2026
This is the key takeaway: 👉 Immunometabolic microglia depend on lactate metabolism 👉 Blocking LDH collapses this state This is not just modulation— it’s state-specific vulnerability
110
Shannon Macauley @macauleylab.bsky.social · 01/05/2026
And critically: 🔥 Selective depletion of disease-associated microglia → ↓ Clec7a⁺ → ↓ CD68⁺ → ↓ peri-plaque microglia
110
Shannon Macauley @macauleylab.bsky.social · 01/05/2026
Importantly!!! We can block LDH and: ✔ ↓ brain lactate (~60%) ✔ ↓ ISF Aβ (~50%)
110
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.
110
Shannon Macauley @macauleylab.bsky.social · 01/05/2026
A lot of LDHA is extracellular, but the microglia surrounding plaques are highly glycolytic (LDHA+)
110
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
110
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
110
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.
110
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...
Fig1
110
Shannon Macauley @macauleylab.bsky.social · 01/05/2026
New Paper Alert! From @clairashley.bsky.social in the lab! Alzheimer’s disease isn’t just protein aggregation. It’s an immunometabolic disorder. Our new work shows: 👉 Lactate is not a byproduct 👉 It’s a driver of microglial dysfunction and Aβ dynamics link.springer.com/article/10.1...
link.springer.com
Lactate metabolism links reactive microglia, amyloid pathology, and Aβ dynamics - Journal of Neuroinflammation
Journal of Neuroinflammation - Alzheimer’s disease (AD) is increasingly recognized as a disorder of early immunometabolic dysfunction, yet how amyloid-β (Aβ) pathology reshapes...
1125
Shannon Macauley @macauleylab.bsky.social · 23/04/2026
Beautiful!!!🤩
110
Reposted by Shannon Macauley
Melissa Cooper, PhD @melcooperphd.bsky.social · 22/04/2026
Astrocytes do so much more than any of us thought - they even communicate among specific brain regions across hemispheres! The journey to this paper spanned nearly a decade, but I'm most excited to see what everyone else does with the tools we've built. There's so much for all of us to explore!
nature.com
Astrocytes connect specific brain regions through plastic networks - Nature
Communication between distant brain regions is mediated by plastic networks of gap junction-coupled astrocytes.
1016475
Shannon Macauley @macauleylab.bsky.social · 17/04/2026
Accepted! Can’t wait to share this work! Way to go, @clairashley.bsky.social !
271
Reposted by Shannon Macauley
Nature Portfolio @natureportfolio.nature.com · 12/04/2026
A study in Nature Aging shows that the strongest Alzheimer’s Disease risk gene, APOE4, can make certain brain cells in young mice hyperactive, which can predict later memory decline. The study also implicates Nell2 protein as a contributor to APOE4-driven dysfunction. #Alzsky 🧬🧪
go.nature.com
Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer’s disease pathogenesis - Nature Aging
Young, cognitively normal APOE4 mice display hippocampal network hyperactivity that predicts later memory decline. This phenotype is driven by neuronal APOE4 expression, which causes hyperexcitability of hippocampal neurons and can be reversed by targeting Nell2.
2335
Shannon Macauley @macauleylab.bsky.social · 10/04/2026
This. 👇 its relentless.
020
Reposted by Shannon Macauley
Zhixing Chen @zhixingchen2.bsky.social · 04/04/2026
See how PKMito dyes promote mitochondrial research😀 @spirochrome.com
0113
Reposted by Shannon Macauley
Waggoner Lab @labwaggoner.bsky.social · 25/03/2026
Mitochondrial lactate venting limits oxidative stress @cp-cellmetabolism.bsky.social www.cell.com/cell-metabol...
042
Reposted by Shannon Macauley
Eric Topol @erictopol.bsky.social · 23/03/2026
Even small differences in sleep, physical activity and nutrition (SPAN) can have significant favorable impact vs major adverse cardiovascular events academic.oup.com/eurjpc/advan...
513130
Reposted by Shannon Macauley
UK Sanders-Brown Center on Aging @uksbcoa.bsky.social · 20/03/2026
Shining bright at #ADPD2026! Members of the @macauleylab.bsky.social share their findings! @ukresearch.bsky.social
Clair Ashley presents her poster at the AD/PD Advances in Science & Therapy Conference.Sierra Turner presents her poster at the AD/PD Advances in Science & Therapy Conference.Riley Irmen presents during the AD/PD Advances in Science & Therapy Conference.Sierra Turner, Riley Irmen, & Clair Ashley stand beside the canal in Nyhavn (New Harbour), Copenhagen, Denmark.
033
Shannon Macauley @macauleylab.bsky.social · 21/03/2026
Look at @rileyirmen.bsky.social , @clairashley.bsky.social , and Sierra Turner go!!!!
010
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!
030
Shannon Macauley @macauleylab.bsky.social · 17/03/2026
Thanks for having me!
020
Shannon Macauley @macauleylab.bsky.social · 15/03/2026
Ouch
021
Reposted by Shannon Macauley
Nature Medicine @natmed.nature.com · 06/03/2026
In this phase 2, randomized trial in early #Alzheimers disease, the #TREM2 agonistic antibody AL002 showed target engagement but did not meet the primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes. #microglia #AD www.nature.com/articles/s41591-026-…
nature.com
The TREM2 agonistic antibody AL002 in early Alzheimer’s disease: a phase 2 randomized trial - Nature Medicine
In this phase 2, randomized trial in early Alzheimer’s disease, the TREM2 agonistic antibody AL002 showed target engagement but did not meet the primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes score.
032
Reposted by Shannon Macauley
Jeremy Berg @jeremymberg.bsky.social · 01/03/2026
NSF Update (Awards through 2/27/26) Directorates to follow 1/10
A line graph showing NSF grant awards made through 2/27/26 for fiscal year 2026 compared with grant awards for fiscal years 2021-2025.
30675445
Shannon Macauley @macauleylab.bsky.social · 03/03/2026
Proud to have our work on tau, metabolism, and sleep highlighted by the University of Kentucky! Thanks again to the NIH, CART Fund, and @brightfocus.bsky.social for supporting our work. uknow.uky.edu/research/uk-...
uknow.uky.edu
UK researchers discover brain’s energy ‘hijacked’ by Alzheimer’s protein
Scientists at the University of Kentucky have uncovered a new reason why people with Alzheimer’s disease often struggle with sleep, long before memory loss begins. The study, led by researchers at the...
0114
Reposted by Shannon Macauley
Jeremy Berg @jeremymberg.bsky.social · 26/02/2026
New and Competitive Renewals Only 803 grants have been made compared to ~2650 in fiscal years 2023 and 2024 through February 20. All institutes and centers (include OD now) have made awards except NIAAA, NLM, NCCIH, and FIC. 3/4
Line graph of the number new and competitive renewal grants funded by NIH in fiscal year 2026 through February 20, compared to fiscal years 2020-2025. The fiscal year 2026 is well below the other curves.
42225
Reposted by Shannon Macauley
Jeremy Berg @jeremymberg.bsky.social · 26/02/2026
My weekly update on NIH All projects 1/4
Line graph of the number of NIH projects funded by NIH in fiscal year 2026 through February 20, compared to fiscal years 2020-2025. The fiscal year 2026 is following the curve for fiscal year 2025 but offset due to the government shutdown that occurred at the beginning of the fiscal year.
33023
Shannon Macauley @macauleylab.bsky.social · 03/03/2026
In case you’re curious how 2026 is going…. Way worse than 2025!
010
Reposted by Shannon Macauley
Charleston Conference on Alzheimer's Disease (CCAD) @the-ccad.bsky.social · 28/02/2026
Nothing says Charleston like an evening at Bowens Island Restaurant! After a full day of presentations, oysters and a Lowcountry boil were the perfect way to unwind and connect outside the conference room. 🦪 🦐 #CCAD2026
141
Shannon Macauley @macauleylab.bsky.social · 18/02/2026
A little crowd sourcing exercise- if you could listen to one researcher talk about brain metabolism, who would it be?
000
Reposted by Shannon Macauley
bioRxiv Neuroscience @biorxiv-neursci.bsky.social · 17/02/2026
Human Cerebral Cortex Organization Characterized by Functional PET-FDG "Metabolic Connectivity" www.biorxiv.org/content/10.64898/20…
021
Shannon Macauley @macauleylab.bsky.social · 03/02/2026
www.nature.com/articles/s41...
nature.com
Spatial FBA reveals heterogeneous Warburg niches in renal tumors and lactate consumption in colorectal cancer - npj Systems Biology and Applications
npj Systems Biology and Applications - Spatial FBA reveals heterogeneous Warburg niches in renal tumors and lactate consumption in colorectal cancer
010
Reposted by Shannon Macauley
PLOS Biology @plosbiology.org · 03/02/2026
Finally, on a more holistic level, Guang Sheng Ling and colleagues suggest a two-pronged approach to targeting #immunometabolism therapeutically through pharmaceutical and lifestyle interventions, with a focus on #cancer plos.io/4jNASKk
plos.io
Targeting immunometabolism in cancer through pharmacological and lifestyle interventions
Immunometabolism is often disrupted in diseases such as cancer, suggesting it could be useful target for therapy. This Essay explores the potential for incorporating both lifestyle changes and drug th...
002
Shannon Macauley @macauleylab.bsky.social · 03/02/2026
Your organization's data cannot be pasted here.
000
Reposted by Shannon Macauley
Shannon Macauley @macauleylab.bsky.social · 23/01/2026
New work from our lab! Link: rdcu.be/e0sfU 𝗧𝗮𝘂 𝗛𝗶𝗷𝗮𝗰𝗸𝘀 𝗕𝗿𝗮𝗶𝗻 𝗠𝗲𝘁𝗮𝗯𝗼𝗹𝗶𝘀𝗺, 𝗗𝗿𝗶𝘃𝗶𝗻𝗴 𝗦𝗹𝗲𝗲𝗽 𝗟𝗼𝘀𝘀 𝗶𝗻 𝗔𝗹𝘇𝗵𝗲𝗶𝗺𝗲𝗿’𝘀 𝗗𝗶𝘀𝗲𝗮𝘀𝗲 A quick thread on our findings!
rdcu.be
Tau pathology reprograms glucose metabolism to support cortical hyperexcitability, excitatory/inhibitory imbalance, and sleep loss
npj Dementia - Tau pathology reprograms glucose metabolism to support cortical hyperexcitability, excitatory/inhibitory imbalance, and sleep loss
2135
Shannon Macauley @macauleylab.bsky.social · 24/01/2026
Thanks, Misha! Would love your thoughts. We're interested in how this layers on with APOE!
010
Shannon Macauley @macauleylab.bsky.social · 23/01/2026
Thanks to my funders: NIH, NIA, BrightFocus, CART Fund
000