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38/100

✓ Peer-reviewed alzhub usefulness score 38 out of 100. Treatments

Topic: Brain proteins, microglia and lab models

The blood-brain barrier (BBB) displays a highly organized and complex structure, which is important for maintaining brain homeostasis and protecting the brain from foreign molecules or pathogens. Receptor-mediated transcytosis (RMT) is one of the main delivery pathways across the BBB for molecules that cannot pass the barrier via, e.g. paracellular diffusion. For understanding the treatment options in neurodegenerative diseases such as Alzheimer´s disease (AD), it is important to investigate transport pathways and mechanisms at the BBB for a potential delivery of drugs, antibodies or other compounds across the BBB. This review provides an overview of the different transport variants across the BBB and how they can be targeted in order to promote internalization or secretion into or out of the brain. Therefore, we want to focus on two characterized proteins: the low-density lipoprotein receptor-related protein 1 (LRP1), which is a key mediator of amyloid β (Aβ) clearance from the brain during AD, and transferrin receptor 1 (TfR1), which is already used as a target for antibody-delivery into the brain. Additionally, this review discusses two other important proteins, which have been less frequently addressed in research regarding transport mechanisms: P-glycoprotein (P-gp) as another transporter at the BBB and proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol homeostasis which promotes the degradation of the low-density lipoprotein receptor (LDLR) and LRP1. For these four main proteins, we aim to highlight existing approaches for targeting or inhibiting the aforementioned receptors or proteins. The approaches enable a higher penetration of the BBB, a better distribution in the brain, and ultimately fewer side effects of antibodies or nanoparticles. Here, we include lecanemab, trontinemab, dual TfR/CD98hc shuttles, evolocumab and alirocumab, immunoliposomes and other nanoparticles targeting TfR1 or LRP1. We will further highlight approaches which differ from these common ideas and demonstrate the current state of the art regarding drug delivery and waste clearance across the BBB.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Gröbner, L. S., & Pietrzik, C. U. (2026). Transport pathways across the blood-brain barrier for waste clearance and drug delivery. Fluids and Barriers of the CNS. https://doi.org/10.1186/s12987-026-00812-7

Vancouver

Gröbner LS, Pietrzik CU. Transport pathways across the blood-brain barrier for waste clearance and drug delivery. Fluids and Barriers of the CNS. 2026. doi:10.1186/s12987-026-00812-7. PMID: 42143322.

BibTeX

@article{grobner2026-42143322,
  author  = {Gröbner, Lea S. and Pietrzik, Claus U.},
  title   = {{Transport pathways across the blood-brain barrier for waste clearance and drug delivery}},
  journal = {Fluids and Barriers of the CNS},
  year    = {2026},
  doi     = {10.1186/s12987-026-00812-7},
  pmid    = {42143322},
  url     = {https://doi.org/10.1186/s12987-026-00812-7}
}

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Key findings

Additionally, this review discusses two other important proteins, which have been less frequently addressed in research regarding transport mechanisms: P-glycoprotein (P-gp) as another transporter at the BBB and proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol homeostasis which promotes the degradation of the low-density lipoprotein receptor (LDLR) and LRP1.
For these four main proteins, we aim to highlight existing approaches for targeting or inhibiting the aforementioned receptors or proteins.
The approaches enable a higher penetration of the BBB, a better distribution in the brain, and ultimately fewer side effects of antibodies or nanoparticles.
Here, we include lecanemab, trontinemab, dual TfR/CD98hc shuttles, evolocumab and alirocumab, immunoliposomes and other nanoparticles targeting TfR1 or LRP1.
We will further highlight approaches which differ from these common ideas and demonstrate the current state of the art regarding drug delivery and waste clearance across the BBB.

Why it matters

This review describes transport pathways across the blood-brain barrier, including receptor-mediated transcytosis, and how they might be targeted to deliver drugs or antibodies into the brain. It focuses on LRP1, a key mediator of amyloid beta clearance in Alzheimer's disease, and TfR1, already used as a target for antibody delivery into the brain, as well as P-gp and PCSK9.

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Study details

Evidence strengthLow

How this study scored 38/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 36 of the 96 points we could judge it on, which is 38 out of 100.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Fluids and Barriers of the CNS)
Journal's citation record	1 / 4	Fluids and Barriers of the CNS: journal h-index 86 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	5 / 5	2026 — within 1 year(s) of the newest study here
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	1 / 7	Cited 3 times (OpenAlex, 2026-10-10)
Citations per year	1 / 5	1.5 citations a year over 2 year(s) since 2026
Impact for its field and year	3 / 6	Cited 7.5× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	0 / 6	No other study in this library cites it
Still being cited	1 / 4	Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	— / 4	OpenAlex's profile for last-listed author Claus U. Pietrzik holds only 4 work(s), too few to judge a track record — left out of this score
Institution's track record	1 / 3	Johannes Gutenberg University Mainz: institution h-index 934 (OpenAlex)
Multicenter collaboration	1 / 3	OpenAlex lists 2 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 42143322)
Free to read	2 / 2	Free to read
Points	36 / 96	Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 36 of the 96 points we could judge it on is 38 out of 100.
Total	38 / 100	—

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Read the original

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