Shannon Macauley

Shannon Macauley

@macauleylab.bsky.social

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

2.8K followers1K following545 posts

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Shannon Macauley
@macauleylab.bsky.social

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.comLactate metabolism links reactive microglia, amyloid pathology, and Aβ dynamics - Journal of NeuroinflammationJournal of Neuroinflammation - Alzheimer’s disease (AD) is increasingly recognized as a disorder of early immunometabolic dysfunction, yet how amyloid-β (Aβ) pathology reshapes...

Shannon Macauley reposted

UK Sanders-Brown Center on Aging
@uksbcoa.bsky.social

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.eduTwo hours of sleep restored: UK researchers make Alzheimer’s breakthroughIn 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 ...
Shannon Macauley
@macauleylab.bsky.social

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

Shannon Macauley
@macauleylab.bsky.social

Conceptually: Amyloid → microglial glycolysis → lactate ↑ → sustains inflammation + alters Aβ dynamics Interrupt lactate → ❌ immunometabolic microglia ❌ Aβ signaling axis

Shannon Macauley
@macauleylab.bsky.social

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

Shannon Macauley
@macauleylab.bsky.social

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

Shannon Macauley reposted

Melissa Cooper, PhD
@melcooperphd.bsky.social

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.comAstrocytes connect specific brain regions through plastic networks - NatureCommunication between distant brain regions is mediated by plastic networks of gap junction-coupled astrocytes.

Shannon Macauley reposted

Nature Portfolio
@natureportfolio.nature.com

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.comNeuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer’s disease pathogenesis - Nature AgingYoung, 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.
Shannon Macauley
@macauleylab.bsky.social

This. 👇 its relentless.

Jason Shepherd@jasonsynaptic.bsky.social

It’s brutal in academia right now. A lot is out of our control, but it doesn’t cost anything to remember that there are humans behind papers and grants…reviewers, program officials and funders can be more empathetic in the face of unprecedented chaos in the US scientific enterprise.

Shannon Macauley reposted

Zhixing Chen
@zhixingchen2.bsky.social

See how PKMito dyes promote mitochondrial research😀 @spirochrome.com

Juan C. Landoni@jclandoni.bsky.social

Our paper is now out in Science! Super excited to share our discovery that #mitochondria #pearling is the elusive mechanism driving the regular distribution and inheritance of #mtDNA nucleoids 🧬 [1/6]

Shannon Macauley reposted

Nature Medicine
@natmed.nature.com

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 https://www.nature.com/articles/s41591-026-04273-1

nature.comThe TREM2 agonistic antibody AL002 in early Alzheimer’s disease: a phase 2 randomized trial - Nature MedicineIn 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.
Shannon Macauley
@macauleylab.bsky.social

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.eduUK researchers discover brain’s energy ‘hijacked’ by Alzheimer’s proteinScientists 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...

Shannon Macauley reposted

Jeremy Berg
@jeremymberg.bsky.social

Replying to @jeremymberg.bsky.social

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

Shannon Macauley reposted

PLOS Biology
@plosbiology.org

Replying to @plosbiology.org

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.ioTargeting immunometabolism in cancer through pharmacological and lifestyle interventionsImmunometabolism 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...

Shannon Macauley reposted

Shannon Macauley
@macauleylab.bsky.social

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.beTau pathology reprograms glucose metabolism to support cortical hyperexcitability, excitatory/inhibitory imbalance, and sleep lossnpj Dementia - Tau pathology reprograms glucose metabolism to support cortical hyperexcitability, excitatory/inhibitory imbalance, and sleep loss