Heidi Jacobs

Very grateful and honored to receive a 2025 Distinguished Investigator award and to be a member of the council of distinguished investigators of The Academy for Radiology & Biomedical Imaging Research @acadrad.bsky.social
www.acadrad.org/wp-content/u...

How prediction error drives memory updating: role of locus coeruleus–hippocampal interactions The brain constantly generates predictions based on one’s knowledge of the world, as captured in memory. When these predictions are in error, our knowledge base must be revised to remain relevant. Her...

How prediction error drives memory updating: role of locus coeruleus–hippocampal interactions: Trends in Neurosciences www.cell.com/trends/neuro...

Molecular hallmarks of excitatory and inhibitory neuronal resilience to Alzheimer’s disease - Molecular Neurodegeneration Background A significant proportion of individuals maintain cognition despite extensive Alzheimer’s disease (AD) pathology, known as cognitive resilience. Understanding the molecular mechanisms that protect these individuals could reveal therapeutic targets for AD. Methods This study defines molecular and cellular signatures of cognitive resilience by integrating bulk RNA and single-cell transcriptomic data with genetics across multiple brain regions. We analyzed data from the Religious Order Study and the Rush Memory and Aging Project (ROSMAP), including bulk RNA sequencing (n = 631 individuals) and multiregional single-nucleus RNA sequencing (n = 48 individuals). Subjects were categorized into AD, resilient, and control based on β-amyloid and tau pathology, and cognitive status. We identified and prioritized protected cell populations using whole-genome sequencing-derived genetic variants, transcriptomic profiling, and cellular composition. Results Transcriptomics and polygenic risk analysis position resilience as an intermediate AD state. Only GFAP and KLF4 expression distinguished resilience from controls at tissue level, whereas differential expression of genes involved in nucleic acid metabolism and signaling differentiated AD and resilient brains. At the cellular level, resilience was characterized by broad downregulation of LINGO1 expression and reorganization of chaperone pathways, specifically downregulation of Hsp90 and upregulation of Hsp40, Hsp70, and Hsp110 families in excitatory neurons. MEF2C, ATP8B1, and RELN emerged as key markers of resilient neurons. Excitatory neuronal subtypes in the entorhinal cortex (ATP8B+ and MEF2Chigh) exhibited unique resilience signaling through activation of neurotrophin (BDNF-NTRK2, modulated by LINGO1) and angiopoietin (ANGPT2-TEK) pathways. MEF2C+ inhibitory neurons were over-represented in resilient brains, and the expression of genes associated with rare genetic variants revealed vulnerable somatostatin (SST) cortical interneurons that survive in AD resilience. The maintenance of excitatory-inhibitory balance emerges as a key characteristic of resilience. Conclusions We have defined molecular and cellular hallmarks of cognitive resilience, an intermediate state in the AD continuum. Resilience mechanisms include preserved neuronal function, balanced network activity, and activation of neurotrophic survival signaling. Specific excitatory neuronal populations appear to play a central role in mediating cognitive resilience, while a subset of vulnerable interneurons likely provides compensation against AD-associated hyperexcitability. This study offers a framework to leverage natural protective mechanisms to mitigate neurodegeneration and preserve cognition in AD.

Thrilled to share that our paper “Molecular hallmarks of excitatory and inhibitory neuronal resilience to Alzheimer’s disease” is now out in Molecular Neurodegeneration!

👉 link.springer.com/article/10.1...

#Alzheimer #Resilience #Neuroscience

Here’s my Fluorescence Friday highlight: just got this beautiful shot from the locus coeruleus in our latest tissue section! You can see astrocytes (in green) glowing and wrapping around tiny blood vessels (in red), with pTau staining (in magenta) lighting up the scene. It’s wild how much is going on in just one microscopic field—so cool to see these markers all together and think about what they mean for brain health and Alzheimer’s research. Loving the chance to peek into these cellular hangouts each week! #FluorescenceFriday #PhDLife #Neuroscience

For #FluorescenceFriday✨ Exploring the beauty of the locus Coeruleus using IF staining: neurons🔵 surrounded by glowing astrocytes🟢 embracing delicate blood vessels🔴, alongside striking pTau signals💗. A vivid reminder of the cellular complexity shaping brain health and disease. #LC #Neuroscience

Speakers for ICON symposium on novel measurement & manipulation approaches for neuromodulatory systems! Sept 19, 11:45 am Room Sé

At #ICON? – Join us tomorrow to hear about novel measurement & manipulation approaches for neuromodulatory systems!
🗓️Sept 19,
🕚11:45 am
🏫Room Sé

#ICON2025 #CogNeuro #AcademicSky #LocusCoeruleus #neuroskyence

Shining the light on the Neuromodulatory Subcortical Systems PIA today! ✨ Explore their 2024-2025 activities and share your thoughts: istaart.alz.org/PIA-reports

Impacts of Environmental Distractions and Interruptions on Unsupervised Digital Cognitive Assessments in Older Adults: Cognitive Ecological Momentary Assessment Study Background: Unsupervised cognitive assessments are becoming commonly used in studies of aging and neurodegenerative diseases. Because assessments are completed in everyday environments and without a p...

New paper from the lab. First author @mwelhaf.bsky.social, now in a TT position at North Carolina A&T. We wanted to know how environmental contexts and self-reported distractions impacted cognitive #EMA in older adults. mhealth.jmir.org/2025/1/e71578 1/n

Photostimulation of locus coeruleus CA1 catecholaminergic terminals reversed Spatial memory impairment in an alzheimer’s disease mouse model - Psychopharmacology Rationale One of the earliest changes associated with Alzheimer’s disease (AD) is the loss of catecholaminergic terminals in the cortex and hippocampus originating from the Locus Coeruleus (LC). This ...

We showed previously that chemogenetic activation of the LC rescues spatial reversal learning in the TgF344-AD rat. New paper follows up and reports that optogenetic stimulation of LC terminals in CA1 also rescues cognitive deficits in 3xTg mouse model of AD. link.springer.com/article/10.1...

GitHub - jmumford/randomise-prep: Generate design matrices, contrasts, and scripts to set up FSL randomise analyses. Generate design matrices, contrasts, and scripts to set up FSL randomise analyses. - jmumford/randomise-prep

Do you ever wish you could just use python to pull together the files and code for running FSL's randomise? Me too! I made this: github.com/jmumford/ran... It will even replace the numbers in the file outputs with contrast names of your choosing (and replace corrp with 1minusp).

Inter-individual variability of neurotransmitter receptor and transporter density in the human brain | bioRxiv www.biorxiv.org/content/10.1...

Age-Related Changes in Curiosity: The Influence of Locus Coeruleus on Information-Seeking Behavior https://www.biorxiv.org/content/10.1101/2025.09.04.674248v1

Maternal separation disrupts noradrenergic control of adult coping behaviors - Neuropsychopharmacology Neuropsychopharmacology - Maternal separation disrupts noradrenergic control of adult coping behaviors

#ThisWeekInNPP

Early life stress profoundly impacts the 🧠 & can result in negative affective behaviors well into adulthood

Here, maternal separation stress produced dysregulated noradrenergic activity in the locus coeruleus (LC) across the lifespan, disrupting LC regulation of coping strategies

We're hiring! We have an open TT faculty position in lifespan neuroscience. I'm not on the committee but happy to answer questions about the department and TAMU more generally (I also co-chaired similar searches the last two years). Come join us, please share widely. apply.interfolio.com/172150

I'm thrilled that our paper "Personalised regional modelling predicts tau progression in the human brain" is finally published in PLoS Biology!

Here's a short thread about the main findings of the paper...

Spontaneous pathology in PS19 tauopathy mice progresses via brain networks AbstractTauopathies are progressive neurodegenerative diseases characterized by cellular accumulation of the microtubule-associated protein tau. Evide…

www.sciencedirect.com/science/arti...

Adaptive learning is coordinated across behaviour, time and neurobiology (from synapses and dendrites, to astrocytes and the systems level).

If you’ve ever wondered how noradrenaline helps shape these multiscale learning processes, you might like this: www.cell.com/trends/cogni...

Deadline for these jobs is 5th September, so you've got until next week on Friday to apply! Come join us in beautiful York, complete with Minsters, snickelways, fMRI and OPMs - what more could you ask for?!

#neuroskyence #neurojobs #psychscisky #cognition #psychjobs

REM Sleep Misfires: Intruding Delta Waves Forecast Tau, Amyloid, and Forgetting in Aging Rapid Eye Movement (REM) sleep degrades with age, and more severely in Alzheimer's disease (AD). REM sleep comprises about twenty percent of adult sleep, alternates between phasic and tonic periods, a...

Fresh results now in bioRxiv! 🎉 We know about the function of NREM sleep for overnight memory consolidation. But what about REM sleep? We found that in aging, slow delta waves can intrude phasic REM periods, and this, is associated with worse overnight consolidation 🧠 (1/5) doi.org/10.1101/2025...

📣 We’re recruiting 1-2 postdocs to the incredible WBHI team to lead projects mapping brain & behav’l changes across major endocrine transitions—from adolesc to pregnancy to menopause. Expertise in MRI & human subjects necc. Please reach out to info@wbhi.ucsb.edu and learn more at wbhi.ucsb.edu 🌊

Position open for a neuroimaging focused postdoc to come work with us in Sydney

Feel free to get in touch for a chat if you have any questions about it :)

usyd.wd105.myworkdayjobs.com/en-GB/USYD_E...

Interested in Network hubs, cortical hierarchies, and gradients? Ever wonder where they come from? Check our latest review, where we cover different approaches to mapping hubs, models for their evolution, and mechanisms for how they develop:

osf.io/preprints/os...

not even my area but I can appreciate how cool this work is! 🤯

Great talk by Elouise Koops on the relationship between locus coeruleus-entorhinal tract integrity and tau in ADAD!! #AAIC25 🔵. Collaboration with @ytquiroz.bsky.social

@leatgrinberg.bsky.social relating vulnerability in the NSS to sleep in atypical vs typical AD!! #AAIC25

The Minnesota ultra-high-field meeting will again offer the popular hands-on layer-fMRI analysis pre-workshop on practical aspects.
October 13th-14th 2025.
Registration: sites.google.com/umn.edu/2025...

If you are at #AAIC25, check out Ji-Hyun Kim's posters presenting our new #BrownMICAAD data on #LocusCoeruleus integrity, neural activity, & cognition in young & clinically intact older adults!

Mon (7/28) #455, #967 #OhLabBrown #fMRI #LCscan #XiaoyangHu #JasmineRanieri @heidijacobslab.bsky.social

Really appreciate the #AAIC2025 plenary starting with @alzassociation.bsky.social CEO Joanne Pike saying about the US government’s dramatic cutting of research funds: “We share your outrage”.

Pupil-linked arousal, cortical activity, and cognition in Alzheimer’s disease Combining pupillometry, EEG and MRI, David et al. report abnormalities in tonic and phasic arousal in Alzheimer’s disease. Locus coeruleus integrity, peak

Great (and lots of) work from Mike David and many colleagues using #pupillometry #EEG #MRI to understand arousal and #locuscoeruleus changes in #AlzheimersDisease. Out now in @braincomms.bsky.social
academic.oup.com/braincomms/a...

Earlier Detection of Alzheimer’s Could Help Reduce Its Most Devastating Effects Heidi Jacobs, PhD, is a leader in Alzheimer’s disease research whose personal experience with the disease strengthens her passion for finding a cure — something she is well on her way to achieving.

Learn about our work towards earlier detection of Alzheimer's disease. Despite NIH-funding being delayed, terminated, and uncertain, we are fiercely committed to these goals! Link for donations to support our work is at the bottom of the page, or reach out.
giving.massgeneral.org/stories/earl...

Neuropeptide Y neurons surrounding the locus coeruleus inhibit noradrenergic system activity to reduce anxiety Endogenous neuropeptide Y signaling modulates locus coeruleus activity, promoting adaptive responses to stress.

Beyond happy & proud to have our paper on peptidergic neuromodulation of the #LC out!

This is a project that started with naive intentions & silly curiosity, withstood 1 pandemic & 2 lab moves & made us fall in ❤️ with the most beautiful brain regions of all!! 🔵

www.science.org/doi/10.1126/...