Special thank yous to: Eloise Kok , Pekka Karhunen, Deidre Jansson, Danny Reich, Tony Wyss-Coray, Dorothy Schafer, David Holtzman, and their labs.

We are grateful to all collaborators for their contributions to the study led by Huixin Xu & Peter Lotfy, Benjamin Englert & Janie Oberhauser, and co-senior authors: Jose Ordovas-Montanes, Liisa Myllykangas, Andrew Yang and Maria Lehtinen.

This ChP atlas integrates single-nucleus transcriptomics, AI-assisted quantitative histopathology in >500 postmortem samples, spatial transcriptomics, and mouse studies, defining ChP dysfunction in aging and AD and proposing a macrophage–fibroblast–epithelial barrier axis driving pathology.

Multi-modal choroid plexus pathology in aging and Alzheimer’s disease Brain barriers, cerebrospinal fluid (CSF) dynamics, and peripheral factors are implicated as significant contributors to Alzheimer’s disease (AD). The choroid plexus (ChP) is a blood-brain interface t...

New BioRxiv Post‼️
A Multi-Modal atlas combining human pathology, mouse modeling, transcriptomics, and advanced imaging.
Check out the pre-print here: www.biorxiv.org/content/10.6...

Funded by NIH, NSF, @hhmi.org, William Randolph Hearst Foundation, @bostonchildrens.bsky.social, @simonsfoundation.org Autism Research Initiative, @harvardbrainsci.bsky.social, @hfspo.bsky.social, NYSCF, & more! Grateful to the public and private institutions that made this possible.

HUGE thank you to our collaborators on this project, without whom none of this beautiful work would be possible: Joshua Head, Fred Shipley, Neil Dani, Olga Chechneva, Michael Holtzman, Cameron Sadegh, and Towia Libermann. ‪

We uncovered a new serotonergic axis — from the ChP to the CSF — that sculpts the developing brain. It’s powerful, fast, and vulnerable to disruption. This work opens a new window into how maternal environments influence lifelong brain function.
📖 Full paper: rdcu.be/eoaSY

Maternal exposure to the psychedelic LSD triggered the same ChP secretory response. Within 30 minutes, nearly 70% of embryonic ChP cells formed aposomes.
This suggests serotonergic drugs in pregnancy may directly alter brain development via the CSF.

These brain changes translated into long-term behavioral effects.
Mice exposed in utero to repeated ChP activation showed:
⬇ Less social interaction
⬇ Fewer repetitive behaviors
– Altered courtship vocalizations
Neurodevelopmental outcomes, shifted before birth.

Apocrine secretion didn’t just reshape the cortex, it altered proliferation in the lateral ganglionic eminence (LGE) too. We saw shifts in interneurons, glia, and microglia.
This pathway impacts multiple brain regions and cell types during development.

When we triggered ChP secretion during neurogenesis, the consequences were striking.
We saw shifts in neuronal fate:
⬆️ SATB2+ callosal projection neurons
⬇ TBR1+ corticothalamic neurons
These changes were layer-specific — reorganizing cortical architecture at its foundation.

Apocrine secretion changes the composition of the CSF in minutes. We found a surge of key developmental signals including IGF2, Sonic Hedgehog (SHH), insulin, & transthyretin (TTR). Each of these proteins is known to shape how neural progenitors divide and differentiate.

So what sets off this secretory burst? Among other things, activation of the serotonin receptor 5-HT2C. We showed that stimulating 5-HT2C triggers a wave of calcium signaling followed by apocrine secretion in the embryonic ChP, flooding the CSF with key developmental signals.

Balloon-like structures, called aposomes, form at the surface of ChP cells & release huge amounts of protein directly into the CSF. This is a high-volume, coordinated secretion mechanism, & it massively expands our understanding of how the ChP contributes to brain development.

We discovered the choroid plexus (ChP) doesn’t just secrete tiny vesicles & exosomes. It also unleashes large apocrine secretory structures packed with proteins that flood cerebrospinal fluid (CSF) during brain development. This changes how we think about embryonic brain signaling.

Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development Nature Neuroscience - The choroid plexus (ChP) provides molecular cues for brain development. However, the underlying mechanisms are unclear. This study identifies an apocrine secretion mechanism...

Led by @scienceyael.bsky.social & out today in @natneuro.nature.com: the brain's fluid-secreting organ — the choroid plexus — can reshape neural development through a powerful, little-known process. & it can be hijacked by serotonergic drugs like LSD. 🧠👇 A thread
rdcu.be/eoaSY