Name: Frontier Score for "An astrocyte-microglia MFG-E8 axis promotes synapse engulfment in early amyloid pathology"
Rating: 70
Author: Frontier

What it is

Losing synapses in particular brain regions is an early hallmark of Alzheimer's disease, but what makes those synapses vulnerable in the first place is unclear. In a mouse model of amyloidosis, the authors identify an early state of astrocytes, the brain's support cells, that appears in vulnerable regions before widespread plaque deposition and overt gliosis (the reactive swelling of glial cells). These astrocytes have bulbous-looking processes around synapses, enriched in p62 and glycogen, with impaired autophagy and calcium signalling and reduced contact with synapses. Rather than eating more synapses themselves, they show elevated MFG-E8 (milk fat globule-epidermal growth factor 8) and sit next to increased engulfment of synapses by microglia, the brain's immune cells. Switching astrocyte MFG-E8 up and down shows that it is required for that microglial engulfment and acts through β3 integrin signalling on the microglia. Deleting Mfge8 from astrocytes reduces engulfment and synapse loss across amyloidosis models, and is associated with reduced amyloid pathology, gliosis and cognitive impairment.

Why it matters

It names a signal from one cell type that another cell type needs in order to destroy the synapses beside it, and deleting it in mice protects synapses. In the preprint these bulbous astrocytes build up with age in normal mice too, and by 6 months, a key time point of synapse loss, there are significantly more of them in the model's hippocampus than in wild type, well before the plaques it does not accumulate robustly until 12 to 15 months. Even in 20-month-old, plaque-laden brains they sit well away from the deposits (60 micrometres median distance), so they are not a peri-plaque phenotype. Knocking MFG-E8 down in astrocytes there brought both microglial engulfment and synapse numbers back to near normal.

How to read this

This is a mouse result about a signalling step, not a treatment. The Neuron version is paywalled, so the detail here comes from the authors' bioRxiv preprint, where the knockdown is a CRISPR construct injected into one hemisphere at 4 months, before the earliest reported synapse loss, with 8 male mice per condition in the staining that confirms the knockdown, and only 4 to 6 per condition in the engulfment and synapse counts that carry the result. The preprint's own limitations note that these mice develop neither neurofibrillary tangles nor neurodegeneration, and it says it remains critical to learn whether astrocytic MFG-E8 is ultimately beneficial or detrimental at the circuit level using cognitive assays, which it did not run: the cognitive result above is stated only in the published abstract, and cannot be read from the open version. Its human evidence is limited to MFG-E8 staining overlapping astrocytes in a small post-mortem cohort, which shows presence, not a role. Experiments were split by sex rather than balanced, some male-only and some female-only.

Underlined numbers link to their source. Every metric and quoted figure is listed under Sources and data below.

Filed underNeuroinflammation and Neurodegeneration Mechanisms, Alzheimer's disease research and treatments, Neuroscience and Neuropharmacology Research

Scored 2026-11-12How scoring works

The Frontier Score, in full

How this entry's score is built, term by term. Open any pillar to see each sub-metric's raw value, how it maps to 0 to 100, and a link to its source (OpenAlex for most sub-metrics that combine several sources, NIH iCite where its ratio is part of field-normalized impact).

The three pillars as one shape: a result strong on every axis fills the triangle.

How the Frontier Score is calculated for this breakthrough
Term	Score	Weight	Points
EvidenceHow established and verifiable the result is.	90	× 0.25	22.5
ImpactHow much the result matters, judged field-relative and by current momentum.	48	× 0.25	12.0
NoveltyHow genuinely new the result is, and how fast-moving.	73	× 0.50	36.4
Weighted pillars			70.8
Frontier recency0 months since publication		× 0.98
IntegrityNot retracted		× 1
Frontier Score			70

Confidence: Early signalEarly signal: little citation history yet, so impact is an estimate and may shift as the work is taken up.

Every sub-metric, traced to its source

EvidenceHow established and verifiable the result is.90

Evidence sub-metrics
Sub-metric	Raw value	0 to 100	Weight	Points	Source
Peer review & venueWhether the work has cleared peer review, and how selective its venue is. Peer review is necessary but not sufficient: before citations accrue, a fresh result in one of the five general flagships (Nature, Science, Cell, NEJM, the Lancet) is a stronger evidence signal than one in a selective specialist or society journal, which in turn outranks one in a legitimate but very high-volume mega-journal, and any of them outranks a preprint that has not been reviewed at all.Maps to 0 to 100: Peer-reviewed article graded by venue tier: flagship journal (Nature, Science, Cell, NEJM, the Lancet) 100; selective journal (every other journal the index admits: the specialist journals of those families, JAMA, PNAS, Physical Review Letters and X) 90; high-volume mega-journal (Nature Communications, Science Advances) 78; venue not recorded 88. Other records: review 90, book 70, dataset 60, preprint 45, an article that has not been peer reviewed 45, other 55.	Peer-reviewed, selective journal	90	0.30	27.0	OpenAlex type / primary_location / source
CorroborationIndependent corroboration that the result is on the record and reaching beyond a single source, read as the BREADTH of independent records rather than the size of the citation pile. Counts how many of the five independent citation indices (OpenAlex, Crossref, Semantic Scholar, OpenCitations, Europe PMC) report a citation count for the work at all, zero included, plus orthogonal, non-citation lines of corroboration: citation in Wikipedia, registered clinical trials or clinical citations, released datasets or software or a repository copy, public funding on record, and technical-community discussion. Citation MAGNITUDE is deliberately judged under Impact, not here, so Evidence and Impact measure genuinely different things instead of both rewarding the same citation pile twice.Maps to 0 to 100: Starts at 28 and rises by 9 for each of the five independent citation indices that returns a citation count for the work (zero counts; OpenCitations returns zero even for a DOI it does not hold) and by 6 for each orthogonal non-citation line (Wikipedia, clinical trials or clinical citations, open datasets, software or a repository copy, public funding, community discussion), up to the top of the 0-100 scale.	4 of 5 citation indices report a count, 2 independent non-citation lines	76	0.30	22.8	OpenAlex, Crossref, Semantic Scholar, OpenCitations, Europe PMC, DataCite, NIH RePORTER, Wikipedia, Hacker News count of indices that report a count for the work + orthogonal reach
VerifiabilityHow openly the result can be read, reused, and reproduced. Rewards open access, a Creative Commons BY or CC0 license, a green repository copy anyone can archive, openly minable full text, and released datasets or software a reader can actually run. Cross-checked across OpenAlex, Unpaywall, Europe PMC, and DataCite.Maps to 0 to 100: Closed access 45; open access 88; any Creative Commons BY license (including the NC, ND and SA variants) or CC0 100. A repository copy raises the floor to 85, openly minable full text to 90, and released data or software to 92.	Open access (hybrid), CC-BY, repository copy	100	0.20	20.0	OpenAlex, Unpaywall, Europe PMC, DataCite is_oa / license / has_repository_copy / open datasets
IntegrityRetraction and post-publication correction status. A retracted result is not evidence of anything and collapses the whole Frontier Score; a correction or expression of concern is a softer flag. A correction the publisher labels as its own error (a Publisher Correction) is not a flag on the work. Read across OpenAlex and Crossref (both update-to and updated-by notices).Maps to 0 to 100: Clean 100 (also when the only notice is a Publisher Correction); a correction or expression of concern 75; retracted 0. Flagged if OpenAlex OR Crossref records the notice.	No retraction or concern on record	100	0.20	20.0	OpenAlex, Crossref is_retracted / update-to / updated-by

ImpactHow much the result matters, judged field-relative and by current momentum.48

Impact sub-metrics
Sub-metric	Raw value	0 to 100	Weight	Points	Source
Field-normalized impactImpact relative to the world average for the same field, year, and type, so a small field and a large field are judged fairly. Triangulates three independent field-normalized measures: OpenAlex's Field-Weighted Citation Impact, its citation percentile within the exact field-and-year cohort, and the NIH iCite Relative Citation Ratio. 1.0x is average; the percentile is the share of same-field, same-year work it out-cites.Maps to 0 to 100: Each ratio (1.0 = field average) maps 1.0 to 50, 3.0 to 75, 9.0 to 90; the field+year percentile maps directly (top 1% -> ~99). The available measures are averaged. When none is available yet (very recent work), this sub-metric is left out and Impact is computed from the others.	12.8x FWCI, 1.4x RCR, top 1% of field-year vs field	83	0.45	37.4	OpenAlex, NIH iCite fwci / citation_normalized_percentile / relative_citation_ratio
Influential citationsCitations that genuinely build on the work rather than mention it in passing (Semantic Scholar's influential-citation measure). A sharper signal of real impact than a raw count.Maps to 0 to 100: Saturating: 15 influential citations maps to 50, and none maps to 0. When Semantic Scholar has no measure for the work, this sub-metric is left out and Impact is computed from the others.	0 influential	0	0.20	0.0	Semantic Scholar influentialCitationCount
Citation velocityCitations received in the trailing twelve months (estimated from yearly citation counts: this year's so far plus the share of last year's that falls inside the window), judged as a rate rather than a lifetime total. Momentum is what a frontier index cares about: a result being taken up fast right now is landing, whether its lifetime pile is large or still small. Where an expected field citation rate is known, the momentum is also read relative to it, so a fast-moving result in a quiet field is not overlooked.Maps to 0 to 100: Saturating: 30 citations in the last twelve months maps to 50. When NIH iCite provides the field's expected rate, this is blended evenly with the ratio of observed to expected momentum.	7 in last 12 months (0.7x field rate)	30	0.35	10.6	OpenAlex, NIH iCite counts_by_year / field_citation_rate

NoveltyHow genuinely new the result is, and how fast-moving.73

Novelty sub-metrics
Sub-metric	Raw value	0 to 100	Weight	Points	Source
Conceptual noveltyHow genuinely new the contribution is, measured at publication from the work's OWN content, not its date: how atypical its combination of research areas is versus all prior work, and whether it builds on a broad, deep base rather than only the newest papers in a fast-moving area. This is what separates a real advance from a recent-but-commodity result, and it needs no forward citations, so it is stable for brand-new work. An honestly noisy proxy (even state-of-the-art novelty measures agree only moderately with expert judgment), so it carries bounded weight and never drives the ranking alone.Maps to 0 to 100: Two publication-time signals, each 0-100. The primary one is atypical combination: how unusual the work's median pairing of research topics is versus the prior literature, by pointwise mutual information (a pairing made far more often than chance scores low). The second, foundational reach (the median age of the work's references and the share older than five years), can only lift it: when reach is higher, the score rises by 35% of the gap, and it is never lowered. When only one signal is measurable it is used alone; when neither is (a work too thin in topics or references), this sub-metric is left out and Novelty is computed from the other three. A review is damped to 60%.	Median topic pairing Neuroinflammation and Neurodegeneration Mechanisms x Neuroscience and Neuropharmacology Research (30,327 prior works made this pairing); builds on refs a median 7.7y deep	51	0.45	22.9	OpenAlex topics + referenced_works (publication-time)
RecencyHow recently the work appeared. The frontier is now, so newer scores higher.Maps to 0 to 100: Exponential decay with a 12-month half-life from the publication date.	This month	98	0.30	29.4	OpenAlex publication_date
Attention accelerationWhether attention is rising: citations in the latest full year versus the year before. Accelerating interest signals an active, opening frontier.Maps to 0 to 100: Latest/prior-year ratio: 1x maps to 50, 2x to 75, 4x to 100. The prior year counts as at least 3 citations, so a jump from one citation to a few is not read as explosive growth. With no citations in the latest full year it reads as unknown, and unknown is neutral (50).	2.7x rising	85	0.10	8.5	OpenAlex counts_by_year
Edge of reviewPreprints sit ahead of the peer-review process and brand-new papers have only just cleared it. Both earn novelty here (while a preprint is discounted under Evidence), because that is where the frontier forms first.Maps to 0 to 100: Preprint 95; any other record 80 when under 6 months old, 65 under 18 months, 45 after that.	Peer-reviewed record	80	0.15	12.0	OpenAlex type / publication_date

ProvenanceAll sources

Sources and data

The source figures behind this entry, grouped by the source that holds them: up to five citation indices cross-checked, field-normalized impact, then real-world reach (Wikipedia, community discussion, clinical trials, released data and public funding) where it exists. Each value links to its record.

OpenAlex

Primary record

Total citations: 15
Field-weighted citation impact: 12.8x field average
Citation percentile: Top 1% of its field-year
Citations, recent 12 months: 7
Publication date: 2026-11-01
Access: Open access (hybrid)

Crossref

Citations: 0
Works it builds on: 84
Funders on record: 11

Semantic Scholar

Citations, all versions: 0
Influential citations: 0

OpenCitations

Citations: 0

NIH iCite

Relative Citation Ratio: 1.36 (NIH-funded median 1.0)
Potential to translate: 5%

Unpaywall

Reuse license: CC-BY

NIH RePORTER

NIH grants funding it: 2
NIH award funding: $13,188,349

OpenAlex record Read it in Neuron

Figures quoted in the write-up

Figure	Value	Source
Age at which bulbous astrocytes are raised in the model (Preprint: levels were significantly higher in the NL-F knock-in hippocampus than in wild type, at a key timepoint of synapse loss)	6 months	bioRxiv: the authors' preprint
Age at which this model accumulates plaques robustly (Preprint: the bulbous astrocytes appear prior to robust amyloid-beta plaque accumulation)	12-15 months	bioRxiv: the authors' preprint
Distance between bulbous astrocytes and plaque deposits (Preprint: measured in the plaque-laden 20-month NL-F knock-in hippocampus; little spatial association was found between the p62-accumulated bulbous astrocytes and aggregated amyloid deposits, so they are not a peri-plaque phenotype)	60 μm median proximity distance	bioRxiv: the authors' preprint
Age at which the astrocyte knockdown was injected (Preprint: 8 weeks before the earliest reported synapse loss in this model)	4 months	bioRxiv: the authors' preprint
Mice per condition in the knockdown result (Preprint: a separate panel with n=8 male mice per condition verified the more than 90% drop in MFG-E8 protein in the labelled zone)	n=4-6 male mice (engulfment), n=4-5 (synapse density)	bioRxiv: the authors' preprint

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What it is

Why it matters

The Frontier Score, in full

Sources and data

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Crossref

Semantic Scholar

OpenCitations

NIH iCite

Unpaywall

NIH RePORTER

Show this score where your work lives

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