Good news! Amazing stuff!
It is very surprising to read in the abstract of this paper that in the year 2026 "the scale and function of physiological blood-to-brain protein transport remain largely unknown". Hard to believe!
"... Now, scientists have created an atlas of all the proteins that make the guest list for mouse brains—including one crucial to limiting Alzheimer’s onset.
Researchers used protein-labeling chemistry to tag 861 proteins in mouse blood. Of those, only 92 could pass through the blood-brain barrier. The selection included proteins produced throughout the body, especially in the liver.
Once inside the brain, the different proteins were sent to different kinds of brain cells, where they served specific roles such as maintaining connections between neurons. ..."
"... Multiple organs in the body, such as the liver and kidney, release different proteins into the blood at different times. This means the specific mix of protein types in blood plasma—the liquid portion of the blood—can relay important information to the brain about the current state of the body. But with the blood-brain barrier, which of these proteins can the brain sense? ...
Of the 861 proteins the scientists tracked, the blood-brain barrier only allowed 92 to enter the brain. Most of these proteins were produced in distant parts of the body, especially the liver. The findings suggest that the blood-brain barrier acts as a gatekeeper, using specialized receptors to identify and transport specific plasma proteins from the body into the brain. ...
The team also found that, once inside the brain, different proteins are directed to specific types of brain cells, where they carry out specialized functions. ...
For example, a protein made in the liver travels to the brain to support cells known as astrocytes. Once in the brain, the protein—known as apolipoprotein A1, or APOA1—activates a pathway that maintains healthy connections between neurons. Failure of this pathway has previously been linked to a higher risk of Alzheimer’s disease ..."
From the highlights and abstract:
"Highlights
• Bioorthogonal chemistry and proteomics map the blood-brain barrier transportome
• Each permeable protein homes to distinct brain cell types to support cell functions
• Blood-brain barrier transport dysfunction arises early in Alzheimer’s disease models
• Liver-derived APOA1 engages astrocyte ABCA1 to rescue Alzheimer’s dysfunction in mice
Summary
The blood-brain barrier (BBB) has been defined primarily by what it excludes, yet the scale and function of physiological blood-to-brain protein transport remain largely unknown.
Using bioorthogonal proteomics, we find that the healthy BBB samples 191 plasma proteins and permits 92 into the brain parenchyma. Enriched for carrier and metabolic functions, these proteins home to distinct brain cell types, such as apolipoprotein A1 (APOA1) to astrocytes and alpha-1 antitrypsin (SERPINA1) to microglia.
This cell-type tropism relies on a BBB-parenchyma receptor hand-off: APOA1 crosses the BBB via SR-B1 and engages astrocytic ATP-binding cassette transporter A1 (ABCA1), a key Alzheimer’s risk gene, driving cholesterol efflux that supports synapse integrity. Unlike LPS-induced nonspecific leakage, early-stage 5xFAD mice show selective BBB transport remodeling, with reduced APOA1 and increased SERPINA1 uptake.
Hepatic APOA1 overexpression restores APOA1 in the 5xFAD brain, rescuing astrocytic, synaptic, and behavioral deficits.
These findings recast the BBB as a selective interface that recruits neuroprotective circulatory proteins for brain health."
ScienceAdviser
Study Rewrites the Rules of the Blood-Brain Barrier (original news release) "Gladstone scientists discover the dynamic barrier—long defined by what it excludes—imports an unexpected degree of protective proteins into the brain, revealing a new blueprint for treating Alzheimer’s disease."
Graphical abstract
Figure 1 A bioorthogonal proteomics strategy to detect plasma proteins within the healthy brain