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Cited by 18Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice

Open access
Vargas-Caballero, Mariana, Denk, Franziska, Wobst, Heike J., Arch, Emily, Pegasiou, Chrysia-Maria, Oliver, Peter L., Shipton, Olivia A., Paulsen, Ole +1 more·2017·Frontiers in Neuroscience
DOI 10.3389/fnins.2017.00201PMC PMC5401872
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Abstract

Microtubule associated protein tau (MAPT) is involved in the pathogenesis of Alzheimer’s disease and many forms of frontotemporal dementia (FTD). We recently reported that Aβ-mediated inhibition of hippocampal long-term potentiation (LTP) in mice requires tau. Here, we asked whether expression of human MAPT can restore Aβ-mediated inhibition on a mouse Tau-/- background and whether human tau with an FTD-causing mutation (N296H) can interfere with Aβ-mediated inhibition of LTP. We used transgenic mouse lines each expressing the full human MAPT locus using bacterial artificial chromosome technology. These lines expressed all six human tau protein isoforms on a Tau-/- background. We found that the human wild-type MAPT H1 locus was able to restore Aβ42-mediated impairment of LTP. In contrast, Aβ42 did not reduce LTP in slices in two independently generated transgenic lines expressing tau protein with the mutation N296H associated with frontotemporal dementia (FTD). Basal phosphorylation of tau measured as the ratio of AT8/Tau5 immunoreactivity was significantly reduced in N296H mutant hippocampal slices. Our data show that human MAPT is able to restore Aβ42-mediated inhibition of LTP in Tau-/- mice. These results provide further evidence that tau protein is central to Aβ-induced LTP impairment and provide a valuable tool for further analysis of the links between Aβ, human tau and impairment of synaptic function.

AI snapshot

Written from the paper’s full text.

TL;DR

Wild-type human tau (MAPT-H1) restores Aβ42-mediated inhibition of hippocampal LTP in Tau−/− mice, whereas FTD-associated N296H mutant tau does not. N296H slices show lower basal AT8/Tau5 phosphorylation and resistance to Aβ42-induced LTP impairment.

Key findings

  • In wild-type human tau H1 mice, Aβ42 significantly reduced LTP compared with control (Aβ42 LTP 124.7 ± 6.2, N = 18 vs. control 148.43 ± 5.47, N = 16; post-hoc P < 0.05).
  • In N296H lines, Aβ42 did not reduce LTP: N51 Aβ42 LTP 153.6 ± 6.1, N = 20, P = 0.65 vs. control; N24 Aβ42 LTP 147.3 ± 6.3, N = 6, P = 0.50 vs. control.
  • N296H line N24 showed significantly higher MAPT exon 10 inclusion than H1 (0.78 ± 0.02, N = 2 vs. 0.30 ± 0.005, N = 3; P < 0.05).
  • Basal AT8/Tau5 ratio was lower in N51 than H1 (0.43 ± 0.03 of normalized H1 values, N = 6 each, P < 1 × 10−5), while total tau normalized to GAPDH was 5.4 ± 0.3 times higher in N51 than H1.

Methods

  • Transgenic mice expressed the full human MAPT locus via BAC/PAC on a Tau−/− C57BL/6-J background: wild-type H1, and two independently generated N296H lines (N51, N24); both sexes were used.
  • Acute parasagittal hippocampal slices (400 μm) were incubated with 220 nM human Aβ42 or control ACSF for 1–3 h; CA3-CA1 field recordings measured input-output, paired-pulse ratio, and LTP induced by 100 Hz for 1 s HFS.
  • Molecular analyses included Western blot for tau isoforms after dephosphorylation, RNA in situ hybridization, Sequenom MassARRAY exon 10 splicing, and AT8/Tau5 phosphorylation normalized to GAPDH; data analyzed with ANOVA and paired t-tests.

Limitations

  • The authors state that BAC transgenic technology cannot match exact protein expression across lines; H1 mice had lower tau levels, and low H1 expression caused high variability in Western blots, with Aβ42-induced phosphorylation trends not reaching significance.
  • The authors note that experiments do not address whether N296H affects tau-fyn association or subcellular localization, and other post-translational modifications are not ruled out.
  • Evident from the text: conclusions rely on acute hippocampal slices and LTP only, with no behavioral, cognitive, or in vivo pathology endpoints; mechanistic links to fyn, GSK-3β, and tau oligomers are discussed but not directly tested here.

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

Integrity signals

Registry

Crossref · 10.3389/fnins.2017.00201

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

11 tests recomputed · 1 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

12 of 24 cited sources checked · 6 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Aβ42-mediated inhibition of LTP in wild type mice requires tau.

    “We previously showed that 220 nM Aβ42 inhibits tetanus-induced LTP in wild type mice and that it does not have an effect on LTP in Tau−/− mice (Shipton et al., 2011).”
    • Also stated in: § Introduction · boosted
      “we have previously shown that hippocampal slices from Tau−/− animals are not susceptible to human Aβ42-mediated LTP impairment (Shipton et al., 2011).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Shipton et al., 2011 source
  • Premisecitation

    Aβ42 drives tau phosphorylation at GSK3β epitopes.

    “Aβ42 drives tau phosphorylation at GSK3β epitopes (Jo et al., 2011; Shipton et al., 2011; Mondragon-Rodriguez et al., 2012) by a variety of proposed mechanisms in the Wnt signaling pathway (Purro et al., 2012; Vargas et al., 2014).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Jo et al., 2011

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

    • cites Shipton et al., 2011 source
    • cites Mondragon-Rodriguez et al., 2012 source

      The Results (Figure 1) report that five days of Aβ exposure increased tau phosphorylation at PHF-1 and AT180 in hippocampal slice cultures. The Discussion identifies both as GSK3β target sites. However, our copy calls the treatment Aβ rather than specifically Aβ42, and it reports no Aβ-induced increase at another GSK3β target, AT8; it also does not establish that GSK3β mediated the increase. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Premisecitation

    N296H causes increased inclusion of MAPT exon 10, leading to an overrepresentation of tau isoforms with four microtubule-binding repeats (4R tau).

    “Like many other familial FTD mutations (Denk and Wade-Martins, 2009), N296H causes increased inclusion of MAPT exon 10, leading to an overrepresentation of tau isoforms with four microtubule-binding repeats, known as 4R tau (Grover et al., 2002; Yoshida et al., 2002).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Grover et al., 2002 source
    • cites Yoshida et al., 2002 source
  • Findingown data

    Input-output curves are similar for ACSF and Aβ42 treatment in all three transgenic lines tested.

    “We observed similar input-output curves for both ACSF and Aβ42 treatment in all three transgenic lines tested (Figures 2A–C).”
    • Also stated in: § Results · plain
      “Repeated measures ANOVA between-subjects showed no significant effect of genotype [F(2, 68) = 0.33, P = 0.72] or treatment [F(1, 68) = 0.74, P = 0.39] and no genotype*treatment interaction [F(2, 68) = 0.51, P = 0.49].”
    Quote in the paperNot a substantial claim
  • Findingown data

    Total tau levels normalized to GAPDH are 5.4 ± 0.3 times higher in N51 animals compared with H1 values normalized to GAPDH.

    “We first noted that in control samples total tau levels normalized to GAPDH were 5.4 ± 0.3 times higher in N51 animals compared to H1 values normalized to GAPDH (N = 6 H1, N = 6 N51, P < 1 × 10−5. Figures 3A,B).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 11
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Premisecitation

    Tau phosphorylation results in enhanced dendritic fyn localization coupled to a disruption of the PSD-95/NMDAR interaction and abnormal postsynaptic density ultrastructure.

    “This tau phosphorylation results in enhanced dendritic fyn localization coupled to a disruption of the PSD-95/NMDAR interaction (Mondragon-Rodriguez et al., 2012) and abnormal postsynaptic density ultrastructure (Purro et al., 2012).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites Mondragon-Rodriguez et al., 2012 source

      In “Endogenous Phospho-tau Interaction with Synaptic Proteins” (Fig. 6c), the paper reports that NMDA receptor activation did not change the interaction between PSD95 and the NMDA receptor subunit GluN2B—contrary to the attributed disruption. It reports increased phospho-tau–Fyn interaction and proposes a possible transient increase in synaptic Fyn, but does not establish enhanced dendritic Fyn localization. The ultrastructure claim is attached to a different citation and is not judged here. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites Purro et al., 2012 source

      The section “Dkk1 reduces the size of synapses in mature neurons” (Fig. 3E–F; page not provided) reports electron-microscopy evidence of reduced postsynaptic-density length and area, supporting the cited ultrastructural finding. But it attributes those changes to Dkk1 treatment, not tau phosphorylation; the sentence’s causal link to tau is not supported by this paper. The Fyn and PSD-95/NMDAR portion is attached to a different citation. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    The AT8 phosphorylation levels, synaptic input-output curves, paired-pulse ratios, and hippocampal LTP data presented here are comparable to previous data from wild type and Tau−/− mice.

    “The AT8 phosphorylation levels, synaptic input-output curves, paired-pulse ratios, and hippocampal LTP data presented here are comparable to our previous data from wild type and Tau−/− mice (Shipton et al., 2011).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Shipton et al., 2011 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Aβ plays a permissive role for the spread of tau pathology in vivo.

    “Furthermore, Aβ plays a permissive role for the spread of tau pathology in vivo (Pooler et al., 2015).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Pooler et al., 2015 source

  • May combine two claims.

    Premisecitation

    Reducing tau levels prevents Aβ-induced cognitive deficits and premature mortality, reduces spontaneous and induced seizure activity, and prevents synaptic impairment in mutant APP-expressing mouse models.

    “Reducing tau levels prevents Aβ-induced cognitive deficits and premature mortality, reduces spontaneous and induced seizure activity, and prevents synaptic impairment in mutant APP-expressing mouse models (Roberson et al., 2007, 2011).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Roberson et al., 2007 source
    • cites Roberson et al., 2011 source

  • May combine two claims.

    Premisecitation

    Cultured neurons from Tau−/− mice are not susceptible to Aβ-induced synaptic damage and neurotoxicity.

    “Thus, cultured neurons from tau knockout (Tau−/−) mice are not susceptible to Aβ-induced synaptic damage and neurotoxicity (Rapoport et al., 2002; Nussbaum et al., 2012; Zempel et al., 2013) or to Aβ-induced defects in axonal transport (Vossel et al., 2011).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Rapoport et al., 2002 source
    • cites Nussbaum et al., 2012 source

      In the passage labeled Abstract (page unavailable in our copy), tau-knockout cultured neurons resisted neurotoxicity from pyroglutamylated Aβ oligomers. The paper also reports synaptic effects, but does not show that tau-knockout cultured neurons are protected from Aβ-induced synaptic damage. Its cultured-neuron finding is specific to the tested Aβ preparations, rather than Aβ generally. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Zempel et al., 2013 source

      The discussion reports dramatically reduced Aβ-induced toxicity in TauKO neurons, including protection against microtubule breakdown and mitochondrial mislocalization. But the Results and Figure 6 report that Aβ still caused moderate spine loss in these neurons, so they were not wholly unsusceptible to synaptic damage. Page numbers are not provided in our copy's passages. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Inhibition of the tau kinases CDK5 or GSK-3β reduces Aβ-induced neuronal cell death and malfunction.

    “and inhibition of the tau kinases CDK5 or GSK-3β reduces Aβ-induced neuronal cell death and malfunction (Llorens-Marítin et al., 2014) suggesting that abnormal tau mediates some of the effects of Aβ.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Llorens-Marítin et al., 2014 source

      In “GSK-3β as a Molecular Link Between Aβ and Tau” (page unavailable), the review says GSK-3β inhibition decreases Aβ-induced neurotoxicity in cultured neurons. Its “Synaptic Effects” section also says GSK-3β inhibitors protect synapses from Aβ. The cited passages discuss CDK-5 as a tau kinase but do not establish that inhibiting CDK5 reduces Aβ-induced neuronal death or malfunction. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Paired-pulse ratio at CA3-CA1 synapses shows no effect of genotype or treatment and no genotype × treatment interaction.

    “Two-way ANOVA on paired-pulse data showed no effect of genotype [F(2, 82) = 1.67, P = 0.19] or treatment [F(1, 82) = 0.06, P = 0.81] and no genotype*treatment interaction [F(2, 82) = 0.02, P = 0.98].”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Neither H1 nor N51 AT8/Tau5 ratio following Aβ42 incubation is significantly higher than normalized control levels within the same genotype (H1 P = 0.10; N51 P = 0.96).

    “however, neither H1 nor N51 AT8/Tau5 ratio following Aβ42 incubation was significantly higher than normalized control levels within the same genotype (H1 P = 0.10; N51 P = 0.96; Figure 3C).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The N296H mutation is a splice site mutation that affects the isoform ratio detected in the insoluble fraction of tau fragments from patient brains, leading to an increase in tau isoforms harboring four microtubule-binding repeats (4R).

    “The N296H mutation, in particular, is a splice site mutation that affects the isoform ratio detected in the insoluble fraction of tau fragments obtained from patient brains (Iseki et al., 2001) leading to an increase in tau isoforms harboring four microtubule-binding repeats (4R).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Iseki et al., 2001 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    LTP is a widely accepted cellular model for learning and memory.

    “a widely accepted cellular model for learning and memory (Bliss and Collingridge, 1993)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bliss and Collingridge, 1993 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Control and Aβ42 incubation experiments were interleaved.

    “we interleaved control and Aβ42 incubation experiments and compared the resulting LTP for the three transgenic lines with and without Aβ42.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Under normal conditions the physical tau/fyn association results in targeting of fyn kinase to postsynaptic sites, leading to basal phosphorylation of synaptic NMDARs at Y1472 by fyn.

    “Under normal conditions the physical tau/fyn association results in targeting of fyn kinase to postsynaptic sites (Ittner et al., 2010) leading to basal phosphorylation of synaptic NMDARs at Y1472 by fyn which is notably reduced in Tau−/− mice (Ittner et al., 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ittner et al., 2010 source

  • May combine two claims.

    Interpretationown data

    The N296H mutation in MAPT leads to hypophosphorylation and to a loss of function in the mechanisms that link Aβ42 with impairment of LTP.

    “Our results indicate that the N296H mutation in MAPT leads to hypophosphorylation and to a loss of function in the mechanisms that link Aβ42 with impairment of LTP.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The N296H mutation is associated with frontotemporal dementia (FTD).

    “the disease-associated mutation, N296H, known to lead to frontotemporal dementia (FTD; Iseki et al., 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Iseki et al., 2001 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Tau oligomers produce an acute inhibition of hippocampal LTP and memory.

    “Similarly, tau oligomers produce an acute inhibition of hippocampal LTP and memory (Fá et al., 2016)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fá et al., 2016

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

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Two independently generated N296H transgenic lines (N24 and N51) were used to control for transgene insertion effects.

    “Two lines of N296H P1-derived artificial chromosome (PAC) transgenic mice (N24 and N51) were generated to control for insertion effects.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Each MALDI-TOF assay was repeated eight times in both forward and reverse direction, and N = 2-3 mice were tested per group.

    “Each MALDI-TOF assay was repeated eight times in both forward and reverse direction, and N = 2–3 mice were tested per group.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A control construct expressing a known 1:1 ratio of 4R:3R tau was used for normalization.

    “A control construct expressing a known 1:1 ratio of 4R:3R tau was used for normalization.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The work was carried out under PPL 30/2757.

    “The work was carried out under PPL 30/2757 and all efforts were made to optimize the number of animals used.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Animal care and experimental procedures were conducted in accordance with UK Home Office regulations under the Animals (Scientific Procedures) Act of 1986.

    “Animal care and experimental procedures were conducted in accordance with UK Home Office regulations under the Animals (Scientific Procedures) Act of 1986.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Only slices with a stable baseline (drift <10%) were used for LTP induction.

    “Only slices with a stable baseline (drift <10%) were used for LTP induction.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All efforts were made to optimize the number of animals used.

    “The work was carried out under PPL 30/2757 and all efforts were made to optimize the number of animals used.”
    Quote in the paperNot a substantial claim
22 of 22

  • The authors state this as an assumption.

    The reduction of Aβ42 concentration to 110 nM during perfusion does not cause washout of the Aβ42 effect on plasticity.

    “Perfusion with a half-concentration of the drug continued after slices were transferred to the interface chamber for fEPSP recordings under the assumption that this reduction to 110 nM would not cause a washout of the Aβ42 effect on plasticity.”

  • The paper relies on this without support.

    The H1 haplotype is associated with increased risk of Alzheimer's disease.

    “We chose to express the more common H1 haplotype given its association with increased risk of Alzheimer's disease.”
2 of 2

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value across alpha = .05: F(2, 84) = 2.83, p < .05

    Major

    The paper reports p < .05 here; recomputing from the test statistic and its degrees of freedom gives p = .065. The two fall on opposite sides of alpha = .05. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p < .05 · recomputed p = .065

  • Inconsistent p-value: F(2, 68) = 0.51, p = .49

    Minor

    The paper reports p = .49 here; recomputing from the test statistic and its degrees of freedom gives p = .603. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .49 · recomputed p = .603

2 of 2

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Doesn’t add upF(2, 84) = 2.83reported p < .05 · recomputed p = .065The two fall on opposite sides of .05

    “F(2, 84) = 2.83, p < .05”

  • Doesn’t add upF(2, 68) = 0.51reported p = .49 · recomputed p = .603

    “F(2, 68) = 0.51, p = .49”

  • ConsistentF(2, 68) = 0.33reported p = .72 · recomputed p = .720

    “F(2, 68) = 0.33, p = .72”

  • ConsistentF(1, 68) = 0.74reported p = .39 · recomputed p = .393

    “F(1, 68) = 0.74, p = .39”

  • ConsistentF(2, 82) = 1.67reported p = .19 · recomputed p = .195

    “F(2, 82) = 1.67, p = .19”

  • ConsistentF(1, 82) = 0.06reported p = .81 · recomputed p = .807

    “F(1, 82) = 0.06, p = .81”

  • ConsistentF(2, 82) = 0.02reported p = .98 · recomputed p = .980

    “F(2, 82) = 0.02, p = .98”

  • ConsistentF(2, 84) = 3.11reported p < .05 · recomputed p = .050

    “F(2, 84) = 3.11, p < .05”

  • ConsistentF(1, 84) = 0.82reported p = .37 · recomputed p = .368

    “F(1, 84) = 0.82, p = .37”

  • ConsistentF(1, 32) = 5.27reported p < .05 · recomputed p = .028

    “F(1, 32) = 5.27, p < .05”

  • ConsistentF(2, 32) = 2reported p = .15 · recomputed p = .152

    “F(2, 32) = 2, p = .15”

11 of 11

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.

  • N51 mutation is labeled N256H in Figure 3

    Minor

    The Figure 3 caption identifies line N51 as MAPT-N256H, whereas the results identify N51 as a line carrying the N296H mutation.

1 of 1

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Related

Authors
Vargas-Caballero, M., Denk, F., Wobst, H. J., Arch, E., Pegasiou, C.-M., Oliver, P. L., Shipton, O. A., Paulsen, O., & Wade-Martins, R.
Affiliations
  • King's College London (GB)
  • Tufts University (US)
  • University of Oxford (GB)
  • University of Southampton (GB)
  • University of Cambridge (GB)
ORCID
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2017-04-24
Volume
11
Pages
201-201
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2017.00201
PMC
PMC5401872
OpenAlex
W2609031029
Semantic Scholar
56a0c13620b5e197e0d97a1a99958d57636871c3
Cited by
18
References
37
Citations by year
2024: 1 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 3
FWCI
1.62
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, cc-by)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Wellcome Trust (073141/Z/03/Z)
  • Alzheimer's Society (075406/Z/04/A)
  • CurePSP
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
tau protein, MAPT, amyloid-beta, long-term potentiation, frontotemporal dementia, Alzheimer's disease, tau knockout mice, hippocampus, synaptic function, tau phosphorylation, amyloid-beta 42

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