CoChat
Sign Up
Cited by 54Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

INPP5D deficiency attenuates amyloid pathology in a mouse model of Alzheimer's disease

Open access
Lin, Peter Bor‐Chian, Tsai, Andy Po‐Yi, Soni, Disha, Lee‐Gosselin, Audrey, Moutinho, Miguel, Puntambekar, Shweta S., Landreth, Gary E., Lamb, Bruce T. +1 more·2023·Alzheimer's & Dementia
DOI 10.1002/alz.12849
Open this paper in CoChat — free accountOpen PDF

Abstract

Introduction: Inositol polyphosphate‐5‐phosphatase (INPP5D) is a microglia‐enriched lipid phosphatase in the central nervous system. A non‐coding variant (rs35349669) in INPP5D increases the risk for Alzheimer's disease (AD), and elevated INPP5D expression is associated with increased plaque deposition. INPP5D negatively regulates signaling via several microglial cell surface receptors, including triggering receptor expressed on myeloid cells 2 (TREM2); however, the impact of INPP5D inhibition on AD pathology remains unclear. Methods: We used the 5xFAD mouse model of amyloidosis to assess how Inpp5d haplodeficiency regulates amyloid pathogenesis. Results: Inpp5d haplodeficiency perturbs the microglial intracellular signaling pathways regulating the immune response, including phagocytosis and clearing of amyloid beta (Aβ). It is important to note that Inpp5d haploinsufficiency leads to the preservation of cognitive function. Spatial transcriptomic analysis revealed that pathways altered by Inpp5d haploinsufficiency are related to synaptic regulation and immune cell activation. Conclusion: These data demonstrate that Inpp5d haplodeficiency enhances microglial functions by increasing plaque clearance and preserves cognitive abilities in 5xFAD mice. Inhibition of INPP5D is a potential therapeutic strategy for AD.

AI snapshot

Written from the paper’s full text.

TL;DR

In 5xFAD mice, Inpp5d haplodeficiency reduced amyloid plaque burden and dystrophic neurites, increased microglial Aβ uptake and plaque engagement, and preserved working memory at 6 months. These protective effects were accompanied by TREM2-SYK activation and altered microglial/spatial transcriptomic pathways, suggesting INPP5D inhibition as a potential AD therapeutic strategy.

Key findings

  • Inpp5d haplodeficiency prevented the 6-month cognitive deficit in 5xFAD mice: 5xFAD mice showed reduced spontaneous alternation versus controls, which was absent in Inpp5d−/+:5xFAD animals (n = 20–24 per genotype; p < 0.0001).
  • Inpp5d haplodeficiency reduced diffuse 6E10+ plaques and dense-core X34+ plaques in cortex and hippocampus and decreased LAMP1+ dystrophic neurites (n = 7 per genotype; p < 0.0001). In the subiculum, it reduced the proportion of diffuse plaques and modestly increased the proportion of dense-core plaques.
  • Primary microglia from Inpp5d−/+:B6 mice showed significantly increased fluorescent Aβ1–42 uptake versus Inpp5d+/+:B6 microglia (n = 5 per condition; p < 0.0001), and Inpp5d-haplodeficient 5xFAD mice showed increased Iba1+ and P2RY12+ microglial engagement with X34+ dense-core plaques (n = 6 per genotype; *p < 0.05, *p < 0.001, p < 0.0001).
  • Cortical cytokines showed decreased IFN-γ, IL-1β, and TNF-α and increased IL-10 in Inpp5d-haplodeficient animals (n = 6 per genotype; *p < 0.05, p < 0.01, p < 0.0001); TREM2 expression and SYK phosphorylation were increased, along with microglia-associated genes including Csf1r, Cx3cr1, Ctsd, Cd68, and Mafb. Spatial transcriptomics revealed altered pathways related to protein digestion, synaptic plasticity, calcium signaling, cytokine production, and memory.

Methods

  • 5xFAD mice were crossed with Inpp5d-haplodeficient mice (Inpp5d−/+; 50% reduced Inpp5d expression) to generate a constitutive heterozygous knockout; experimental groups were Inpp5d+/+:B6, Inpp5d−/+:B6, Inpp5d+/+:5xFAD, and Inpp5d−/+:5xFAD, comprising both sexes. Complete knockout mice are not viable beyond 10–12 weeks.
  • Behavioral working memory was assessed by spontaneous alternation in the Y-maze at 4 and 6 months; immunofluorescence used 6E10, X34, LAMP1, NeuN, Iba1, and P2RY12; primary microglial cultures were used for Aβ uptake; cortical cytokines were measured by MSD assay; immunoblotting measured TREM2 and phospho-/total SYK; NanoString nCounter and GeoMx spatial transcriptomics profiled gene expression.
  • Data are mean ± SEM; analyses used Student’s t-test or non-parametric one-way ANOVA with Tukey’s post hoc test, with p < 0.05 significant. Sample sizes included n = 20–24 per genotype for behavior, n = 7 per genotype for plaque density, n = 6 per genotype for microglia/cytokine/immunoblot, n = 3 per genotype for nCounter, and n = 6 per genotype for GeoMx; nCounter used hippocampal RNA from 7.5-month-old female mice, and spatial transcriptomics used 4-month-old animals.

Limitations

  • Stated: future studies are necessary to confirm the mechanisms, and future work should examine Inpp5d in the context of normal APP expression and Aβ production as well as tau pathology. Complete knockout mice are not viable beyond 10–12 weeks, so the study used haplodeficiency.
  • Stated: the authors note a discrepancy with a prior APP/PS1 study in which microglia-specific Inpp5d deletion increased hippocampal plaque burden; they suggest this may result from INPP5D’s role before amyloid deposition begins.
  • Evident: findings rely on a single amyloidosis model (5xFAD) and constitutive haplodeficiency rather than conditional/temporal or other AD models; nCounter profiling used only female mice, limiting sex generalization.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1002/alz.12849

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

8 of 12 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    A non-coding variant rs35349669 in INPP5D increases the risk for Alzheimer's disease (OR = 1.08, 95% CI = 1.06-1.11).

    “a non-coding variant in inositol polyphosphate-5-phosphatase (INPP5D) has been shown to increase AD risk (rs35349669; odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.06-1.11).5,7”
    • Also stated in: § Abstract · plain
      “A non-coding variant (rs35349669) in INPP5D increases the risk for Alzheimer's disease (AD)”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [5] source

      Table 2 (indexed under “Statistical analysis”; page not given) identifies rs35349669 at the INPP5D locus and reports an overall Alzheimer’s disease association with OR 1.08. Its 95% CI is 1.05–1.11, not the claimed 1.06–1.11. The cited passage identifies INPP5D as the closest gene but does not establish that this variant is non-coding or causally increases risk. (LLM, conf=0.91)

      Experimental — accuracy not yet measured
    • cites [7] source

      The Discussion reports that rs35349669 in INPP5D was associated with increased late-onset Alzheimer’s disease risk in the overall meta-analysis (OR = 1.08, 95% CI = 1.06–1.11), but not in the Chinese subgroup. Our copy does not identify the variant as non-coding, so that part of the claim is unsupported. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Premisecitation

    INPP5D regulates microglial functions, including phagocytosis, proliferation, motility, and cytokine release.

    “thereby regulating microglial functions, including phagocytosis, proliferation, motility, and cytokine release.[11][12][13]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [11] source

      The Results and Discussion address TREM2’s effects on phagocytosis and inflammatory factors in HMC3 cells, not INPP5D’s regulation of microglial functions. Searches for INPP5D and SHIP1 found no passage addressing the attributed claim; the paper does not establish the claimed effects on proliferation or motility either. Page numbers were not available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [12]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [13]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Premisecitation

    There is robust Aβ deposition in the subiculum in 5xFAD animals.

    “Given the robust Aβ deposition in the subiculum in 5xFAD animals, 16 we selected this region to analyze the morphology of diffuse (6E10 + , green) and dense-core (X34 + , blue) plaques, along with neuronal abundance using the neuronal nuclear protein (NeuN, red) in matched brain sections (Figure 2A).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [16] source

      The Results section on whole-brain imaging reports that 5XFAD mice have high Aβ plaque densities in the hippocampal formation, which supports the general premise. It does not establish robust deposition specifically in the subiculum; the Results passage that names the subiculum concerns neuronal loss, not plaque density. Page numbers were not available in our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    Upregulated INPP5D levels in peripheral myeloid cells and the brain of LOAD patients indicate that INPP5D is involved in AD pathogenesis.

    “Upregulated INPP5D levels in the peripheral myeloid cells and the brain of LOAD patients indicate that INPP5D is involved in AD pathogenesis.8,9”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [8] source

      The Results section reports increased INPP5D expression in several brain regions of patients with late-onset AD, and the Conclusions link INPP5D to AD pathophysiology. The paper does not report upregulated INPP5D in peripheral myeloid cells from those patients; its myeloid-cell findings concern brain microglia, including in mice. No page numbers are available in our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [9]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Premisecitation

    INPP5D negatively regulates signaling via several microglial cell surface receptors, including TREM2.

    “INPP5D negatively regulates signaling via several microglial cell surface receptors, including triggering receptor expressed on myeloid cells 2 (TREM2)”
    • Also stated in: § INTRODUCTION · plain
      “INPP5D is a negative regulator of signal transduction via immune cell surface receptors.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [10] source

      The Abstract and Discussion state that SHIP1 inhibits TREM2–DAP12 signaling. The Results section on receptor-specific recruitment also reports SHIP1 recruitment after MDL-1 ligation, but not substantial recruitment after SIRPβ stimulation. The experiments described here concern macrophages and osteoclasts, so the claim's extension to several microglial receptors is not established by this paper. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 2
  • May combine two claims. 6
  • The quote only partly states this claim. 1

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Pharmacological inhibition of INPP5D increases microglial proliferation and phagocytic uptake of Aβ peptide and alleviates neuronal loss.

    “Pharmacological inhibition of INPP5D has been shown previously to increase microglial proliferation and phagocytic uptake of Aβ peptide and alleviate neuronal loss.14”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [14] source

      The Results passages (page not provided) report increased microglial proliferation with pan-SHIP1/2 inhibition and increased uptake of Aβ peptide. They also report uptake of neurons that were already dead or apoptotic, not alleviation of neuronal loss. The proliferation result concerns inhibition of both SHIP1 (INPP5D) and SHIP2; SHIP1-selective inhibition did not increase proliferation. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingnone given

    Inpp5d haplodeficiency does not significantly alter microglia coverage in the cortices and hippocampi of 5xFAD mice.

    “The microglia coverage in the cortices and hippocampi was determined (n = 6 per genotype; male, blue; female, red).Statistical analysis was performed by Student's t-test.Data are expressed as the mean ± SEM (standans, not significance).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Inpp5d haplodeficiency elicits distinct spatial transcriptomic profiles in 5xFAD mice.

    “Inpp5d haplodeficiency elicits distinct spatial transcriptomic profiles.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At 6 months of age, 5xFAD mice have reduced spontaneous alternation compared to controls, but this reduction is not observed at 4 months of age.

    “At 6 months of age, 5xFAD mice have reduced spontaneous alternation compared to controls, which is not observed in 4-month-old 5xFAD mice (Figure 1A), consistent with reduced working memory beginning at 6 months.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The 5xFAD mouse model begins to accumulate amyloid pathology at 2 months of age and shows robust amyloid deposition and behavioral impairment after 4 to 5 months of age.

    “The amyloid mouse model, 5xFAD, begins to accumulate amyloid pathology at 2 months of age and shows robust amyloid deposition and behavioral impairment after 4 to 5 months of age.[17][18][19][20]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17][18][19][20]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    Inpp5d haplodeficiency increases the ability of microglia to restrict plaque diffusivity, thereby alleviating plaque-associated neurotoxicity.

    “Inpp5d haplodeficiency reduced the proportion of 6E10 + diffuse plaques (green) and modestly increased the proportion of X34 + dense-core plaques (blue) (Figure 2B), suggesting that Inpp5d haplodeficiency increases the ability of microglia to restrict plaque diffusivity, thereby alleviating plaque-associated neurotoxicity (Figure 1).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: An increased proportion of X34+ dense-core plaques reflects increased plaque compaction and reduced plaque-associated neurotoxicity.

  • May combine two claims.

    Interpretationown data

    Loss of INPP5D is accompanied by reduced plaque burdens and Aβ-associated neuropathology in 5xFAD mice.

    “Overall, these results indicate that loss of INPP5D pre-vents cognitive decline in 5xFAD mice and is accompanied by reduced plaque burdens and Aβ-associated neuropathology.”
    • Also stated in: § 3.1 Inpp5d haplodeficiency protects against cognitive impairment and Aβ accumulation in 5xFAD mice · plain
      “Inpp5d haplodeficiency protects against cognitive impairment and Aβ accumulation in 5xFAD mice”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    INPP5D inhibition augments microglial functions by enhancing motility and phagocytosis and further mitigates disease pathology by activating TREM2 signaling.

    “Our findings in Inpp5d-haplodeficient 5xFAD mice suggest that INPP5D inhibition augments microglial functions by enhancing motility and phagocytosis and further mitigates disease pathology by activating TREM2 signaling.”
    • Also stated in: § HIGHLIGHTS · plain
      “Inpp5d inhibition regulates microglial functions and mitigates amyloid pathology by activating the TREM2 signaling cascade.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Inpp5d haplodeficiency (50% reduced expression) is a valid proxy for INPP5D inhibition.
8 of 8

  • The paper relies on this without support.

    The 5xFAD mouse model recapitulates key aspects of amyloid pathogenesis relevant to Alzheimer's disease.

    “We used the 5xFAD mouse model of amyloidosis to assess how Inpp5d haplodeficiency regulates amyloid pathogenesis.”
    “Here, we crossed a commonly used murine model of AD (5xFAD) with an Inpp5d-haplodeficient mouse strain (Inpp5d -/+ ) to generate a constitutive heterozygous knockout and study the effect of Inpp5d haplodeficiency on Aβ pathogenesis.”

  • The paper relies on this without support.

    Inpp5d haplodeficiency (50% reduced expression) is a valid proxy for INPP5D inhibition.

    “Here, we crossed a commonly used murine model of AD (5xFAD) with an Inpp5d-haplodeficient mouse strain (Inpp5d -/+ ) to generate a constitutive heterozygous knockout and study the effect of Inpp5d haplodeficiency on Aβ pathogenesis.”

  • The paper relies on this without support.

    Findings in 5xFAD mice are predictive of human Alzheimer's disease.

    “Inhibition of INPP5D is a potential therapeutic strategy for AD.”
    “Our results suggest that INPP5D inhibition is a potential therapeutic approach for regulating microglia-mediated AD pathogenesis.”

  • The paper relies on this without support.

    The observed effects of Inpp5d haplodeficiency on amyloid pathology are mediated by microglial INPP5D and not by other cell types or developmental effects.

    “Inpp5d haplodeficiency perturbs the microglial intracellular signaling pathways regulating the immune response, including phagocytosis and clearing of amyloid beta (Aβ).”
    “Inpp5d haplodeficiency increased amyloid uptake and plaque engagement in microglia.”

  • The paper relies on this without support.

    Aβ uptake measured in primary microglia reflects microglial Aβ uptake and its effect on amyloid deposition in vivo.

    “Overall, these results indicate that loss of INPP5D may reduce amyloid deposition by increasing amyloid uptake and decrease plaque-associated neuropathology by increasing plaque compaction.”

  • The paper relies on this without support.

    An increased proportion of X34+ dense-core plaques reflects increased plaque compaction and reduced plaque-associated neurotoxicity.

    “Inpp5d haplodeficiency reduced the proportion of 6E10 + diffuse plaques (green) and modestly increased the proportion of X34 + dense-core plaques (blue) (Figure 2B), suggesting that Inpp5d haplodeficiency increases the ability of microglia to restrict plaque diffusivity, thereby alleviating plaque-associated neurotoxicity (Figure 1).”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Two studies observed no change in plaque burden with reduced Inpp5d levels.

    “While one study reported amelioration of plaque burden by Inpp5d knockdown in a mouse model of AD56, another study reported increased plaque burden78 and two studies observed no change with reduced Inpp5d levels57,61.”

    From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [57]

    Section 3.1 reports that Inpp5d haplodeficiency reduced both diffuse and dense-core plaques in the cortex and hippocampus of 5xFAD mice. The Discussion likewise reports an overall reduction in plaque density, contrary to the attributed finding of no change. (LLM, conf=0.92)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • One mechanism by which SHIP1 deficiency increases the phagocytosis of lipid-rich substrates is through upregulation of TREM2 signaling.

    “We confirmed that one mechanism by which SHIP1 deficiency increases the phagocytosis of lipid-rich substrates is through upregulation of TREM2 signaling (Figures 6D-G, S6E) in line with previous reports55,57.”

    From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [57]

    The TREM2-SYK results section reports increased TREM2 expression and SYK phosphorylation in Inpp5d-haplodeficient 5xFAD mice, and the Highlights report increased microglial amyloid uptake. But the Discussion explicitly calls TREM2 activation as the mechanism a postulate requiring confirmation; the paper does not establish that it causes increased phagocytosis of lipid-rich substrates. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Loss of Inpp5d alters amyloid pathology in models of amyloidosis.

    “Loss of Inpp5d alters amyloid pathology in models of amyloidosis.”

    From Loss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes (2024) · cites this paper as [18]

    The Abstract reports that Inpp5d haplodeficiency increased amyloid plaque clearance in 5xFAD mice, supporting an effect on amyloid pathology. The claim says “models” of amyloidosis, but the paper reports this finding in one model, 5xFAD. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Lin et al. found that deletion of one copy of Inpp5d reduced plaque pathology as measured by immunohistochemical approaches.

    “In contrast to the study by Castranio et al., the deletion of one copy of Inpp5d reduced plaque pathology as measured by immunohistochemical approaches.”

    From Loss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes (2024) · cites this paper as [18]

  • Previous studies of Inpp5d in AD have employed APP transgenic or knock-in models.

    “Previous studies of Inpp5d in AD have employed APP transgenic or knock‐in models to determine the effect of Inpp5d depletion on amyloid pathology. 18 , 19 , 20 , 49”

    From Loss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes (2024) · cites this paper as [18]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Amyloid uptake concentration differs between methods and figure caption

    Major

    The methods specify 0.5 μM labeled Aβ1-42, whereas the caption for the uptake experiment specifies 10 μM.

  • nCounter tissue is identified as hippocampus in methods but cortex in Figure 4

    Major

    The methods say hippocampal RNA was used for nCounter profiling; Figure 4 describes the nCounter results as a comparison of cortices.

  • Cytokine panel is said to quantify 10 cytokines but lists nine

    Minor

    The enumeration contains nine cytokines, not 10.

3 of 3

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Lin, P. B., Tsai, A. P., Soni, D., Lee‐Gosselin, A., Moutinho, M., Puntambekar, S. S., Landreth, G. E., Lamb, B. T., & Oblak, A. L.
Affiliations
  • Indiana University School of Medicine
  • Indiana University Indianapolis (US)
Corresponding author
Oblak, Adrian L.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2022-12-16
Volume
19
Issue
6
Pages
2528-2537
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.12849
OpenAlex
W4311664795
Semantic Scholar
67b983a1274536233577d6e428a6de62ce60d965
Cited by
54
References
28
Citations by year
2026: 10 · 2025: 14 · 2024: 12 · 2023: 18
FWCI
5.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc)
Funders
National Institute on Aging (AG054345, U54 AG054345, K01 AG054753, U54 AG065181)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
INPP5D, inositol polyphosphate 5-phosphatase
MeSH terms
Alzheimer Disease, Amyloid, Animals, Disease Models, Animal, Mice, Transgenic, Phosphoric Monoester Hydrolases, Amyloid beta-Peptides, Microglia, Mice, Plaque, Amyloid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-14.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-14.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review