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

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.

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 🧬🧪

This. 👇 its relentless.

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

Mitochondrial lactate venting limits oxidative stress
@cp-cellmetabolism.bsky.social
www.cell.com/cell-metabol...

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...

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.

Shining bright at #ADPD2026! Members of the @macauleylab.bsky.social share their findings!
@ukresearch.bsky.social

Look at @rileyirmen.bsky.social , @clairashley.bsky.social , and Sierra Turner go!!!!

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!

Thanks for having me!

Ouch

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.

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

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.

NSF Update (Awards through 2/27/26)

Directorates to follow

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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...

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-...

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.

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.

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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.

My weekly update on NIH

All projects

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In case you’re curious how 2026 is going…. Way worse than 2025!

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

A little crowd sourcing exercise- if you could listen to one researcher talk about brain metabolism, who would it be?

Human Cerebral Cortex Organization Characterized by Functional PET-FDG "Metabolic Connectivity" www.biorxiv.org/content/10.64898/2026.02...

www.nature.com/articles/s41...

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...

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

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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

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!

Thanks, Misha! Would love your thoughts. We're interested in how this layers on with APOE!

Thanks to my funders: NIH, NIA, BrightFocus, CART Fund

Big congratulations to our team! @rileyirmen.bsky.social for leading this works. Collabs: @johnsonlab.bsky.social Adam Bauer, Dan Lee, Pat Sullivan, Velu, and all coauthors!

Together, these findings reveal that tau disrupts sleep not by starving the brain of energy, but by misusing or misdirecting it. By linking tau pathology to glycolytic flux , hyperexcitability and sleep loss, this work suggests new targets to restore sleep in Alzheimer’s disease & tauopathies.

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.

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.