Evidence map›Paper›PMID 41559706›Full record

ArticleJournal of neuroinflammation2026

Induction of neurodegeneration in the hippocampus of senescence-accelerated mouse-prone 8 (SAMP8) mice by blood-brain barrier-crossing serum amyloid P component.

Fuka Sato, Ai Fujii, Saki Katagiri, Yuri Uchiumi, Mari Gotoh, Yasunori Miyamoto, Masaki Ishikawa, Yusuke Kawashima, Daisuke Nakajima, Ryo Konno and 4 more

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Fuka SatoInstitute for Human Life ScienceOchanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, Japan.
Ai FujiiInstitute for Human Life ScienceOchanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, Japan.
Saki KatagiriGraduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, Japan.
Yuri UchiumiInstitute for Human Life ScienceOchanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, Japan.
Mari GotohInstitute for Human Life ScienceOchanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, Japan.
Yasunori MiyamotoInstitute for Human Life ScienceOchanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, Japan.
Masaki IshikawaKazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba, Japan.
Yusuke KawashimaKazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba, Japan.
Daisuke NakajimaKazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba, Japan.
Ryo KonnoKazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba, Japan.
Kei YuraInstitute for Human Life ScienceOchanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, Japan.
Keiichi NakagawaDepartment of Pharmacology, National Defense Medical College, 3 - 2 Namiki, Tokorozawa, Saitama, Japan.
Toshiaki IshizukaDepartment of Pharmacology, National Defense Medical College, 3 - 2 Namiki, Tokorozawa, Saitama, Japan.
Kei HashimotoInstitute for Human Life ScienceOchanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, Japan.

Funding

Sasakawa Scientific Research Grant 2023-4001Sasakawa Scientific Research Grant 2025-4010
6 · The paper itself

Abstract

Aging is a major risk factor for neurodegeneration. However, the mechanisms by which age-related disruptions in brain homeostasis induce neurodegeneration remain controversial. To clarify this, we analyzed how age-related changes in blood components induce blood-brain barrier (BBB) structure disruption and neurodegeneration using 6-month-old senescence-accelerated mouse-prone 8 (SAMP8) mice. First, we found that 6-month-old SAMP8 mice showed a decline in learning and memory abilities. We used the senescence-associated β-galactosidase marker to visualize which brain regions were responsible for the behavioral change, showing that the hippocampus had a drastic accumulation of senescence-associated β-galactosidase in SAMP8 mice. Next, we performed multi-omics profiling, which demonstrated that SAMP8 mice showed remarkable changes in the expression of BBB maintenance and immune system-related genes at the early stage of aging. Consistent with these results, the structure of occludin-positive tight junctions in the BBB and the number of microglia were altered in the hippocampus of SAMP8 mice. In addition, SAMP8 mice showed an increase in apoptotic hippocampal neurons and a decrease in synaptic density in mossy fibers, leading to impaired learning and memory. Interestingly, proteomic and immunostaining analyses revealed that one of the blood components, the serum amyloid P component (SAP), translocates to the hippocampus while passing through the BBB in SAMP8 mice. In addition, SAP increased BBB permeability by altering the structure of occludin-positive tight junctions, as shown via in vitro analyses. Furthermore, SAP can lead to neuronal cell death and a decline in synaptic density. Overall, our results reveal a previously unrecognized mechanism by which aging induces neuronal death and impairs learning abilities. These results represent an important conceptual advance in that the increase in the serum component SAP disrupts BBB homeostasis, and consequently, SAP leakage into the brain parenchyma leads to neurodegeneration during aging in SAMP8 mice.

Indexed as

AgingBlood-Brain BarrierHippocampusNeurodegenerative DiseasesAnimalsMaleMiceBlood-brain barrierNeurodegenerationSAMP8SenescenceSerum amyloid p component

Identifiers

PMID41559706
PMCPMC12908395

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.