The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index; none of the 55 sources its claims cite is checked for support yet.
Autism, Alzheimer disease, and fragile X
Open accessAbstract
The present review highlights an association between autism, Alzheimer disease (AD), and fragile X syndrome (FXS). We propose a conceptual framework involving the amyloid-β peptide (Aβ), Aβ precursor protein (APP), and fragile X mental retardation protein (FMRP) based on experimental evidence. The anabolic (growth-promoting) effect of the secreted α form of the amyloid-β precursor protein (sAPPα) may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPα levels associate with more severe symptoms of autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 (mGluR5). Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPα level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPα and production of insoluble Aβ would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism.
Overview
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Written from the paper’s full text.
TL;DR
This review proposes that amyloid-β precursor protein (APP), fragile X mental retardation protein (FMRP), and metabotropic glutamate receptor 5 (mGluR5) form molecular links among autism, Alzheimer disease (AD), and fragile X syndrome (FXS). It hypothesizes that excess secreted α form of APP (sAPPα) contributes to brain overgrowth in severe autism and FXS, whereas relatively lower sAPPα and insoluble Aβ production favor degeneration and atrophy in AD.
Key findings
- In a small sample of young children with severe autism and aggression, plasma total sAPP (including sAPPα) was 2 or more times the levels in children without autism and up to 4 times higher than in children with mild autism; an independent laboratory found elevated plasma sAPPα in 60% of known autistic children (n = 25) versus healthy age-matched controls, and a larger follow-up sample confirmed elevated sAPPα in severe autism without coexistent aggression plus significantly reduced Aβ-40 and Aβ-42 (unpublished data, 2011).
- FMRP inhibits APP mRNA translation by binding G quartets in the APP coding region; mGluR5 activation releases this repression and stimulates sAPP secretion. In Fmr1 knockout mice, basal APP translation was increased, mGluR agonist treatment did not increase APP translation, and soluble Aβ-40 and Aβ-42 were significantly higher than in wild-type mice due to elevated APP expression.
- The authors propose that high sAPPα via nonamyloidogenic processing may contribute to macrocephaly and severe autism/FXS phenotypes, while low sAPPα and insoluble Aβ-40/42 would favor a catabolic, degenerative process leading to brain atrophy in AD.
- Seizures are seen in 10%–30% of individuals with autism and frequently in FXS and AD; based on mouse models, the authors speculate seizure etiology may involve overproduction of APP. Macrocephaly affects up to 20% of children with autism.
Methods
- Narrative review and conceptual synthesis of published literature plus the authors’ laboratory data, proposing a framework involving Aβ, APP, and FMRP.
- Evidence discussed includes human plasma samples from autistic and control children, Fmr1 knockout and wild-type mouse synaptoneurosomes, cell culture studies, and unpublished data (2011); no systematic review, meta-analysis, or formal statistical analysis is described.
- Main analysis is interpretive: linking APP/FMRP/mGluR5 signaling to autism, AD, and FXS phenotypes and comparing anabolic versus catabolic APP processing.
Limitations
- Stated: the original autism plasma finding was based on a small sample; some supporting data are unpublished (2011); elevated sAPPα was not found in mild autism and may not be applicable to that population.
- Stated: the model is speculative and hypothesis-generating, and the authors recognize that effects of developmental perturbations can differ from those of FMRP deficiency.
- Evident from the text: as a narrative review, it lacks a systematic search or quality assessment, relies partly on unpublished and cited data, and the independent replication involved only n = 25 autistic children with elevated sAPPα in 60%.
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Claims the paper makes
44 Sources not found · 16 Own interpretation · 5 Own result · 1 Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“Our previous report demonstrated that higher plasma sAPP␣ levels associate with more severe symptoms of autism, including aggression.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > Abstract
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unlike our original study, we also observed significantly reduced levels of A-40 and A-42 in severe autism (unpublished data, 2011).”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > LINKING SAPP WITH AUTISM
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Our findings of high levels of sAPP␣ in some children with autism (unpublished data, 2011) 13,43 recently were corroborated in an independent laboratory.6”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > SUMMARY, POSSIBLE DRUG TARGETS, AND FUTURE PERSPECTIVES
What the sources say
- Not matchedcites [13]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [43]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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In the paper
“We have reported high levels of total sAPP (including sAPP␣) in plasma of a small sample of young children with severe autism and aggression.13”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > LINKING SAPP WITH AUTISM
What the sources say
- Not matchedcites [13]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, a recent follow-up study by our laboratory in a separate, larger set of autistic and control patient plasma samples confirms our original finding of elevated sAPP␣ in the plasma of severely autistic patients without requiring coexistent aggression (unpublished data, 2011).”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > LINKING SAPP WITH AUTISM
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“There have been recent genetic associations found between cases of autism with pronounced macrocephaly and mutations in the PTEN gene.[40][41]”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > RELATIONSHIPS AMONG NEURONAL PRO-TEINS IN AUTISM, AD, AND FXS
What the sources say
- Not matchedcites [40]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [41]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite our contention that autism spectrum and AD may arise from converse disease mechanisms (especially with respect to APP metabolism), this does not preclude certain therapeutic modalities from proving beneficial in both disorders.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > SUMMARY, POSSIBLE DRUG TARGETS, AND FUTURE PERSPECTIVES
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Elevated neural proliferation is not balanced by increased neural pruning, in part due to FMRP deficiency.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > ROLE OF GENE-ENVIRONMENT INTERACTION IN THE ETIOLOGY OF NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“A recent study 4 showed head growth rate at 30 months was greater for FXS boys with autism (n ϭ 22) than for FXS boys without autism (n ϭ 22).”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > FXS.
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelationaln = 22- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“Further, autism has been associated with DNA hypomethylation in parents.e41”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > ROLE OF GENE-ENVIRONMENT INTERACTION IN THE ETIOLOGY OF NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS
What the sources say
- Not matchedcites e41
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
- It may state two separate claims as one. 21
- Probably not a substantial claim. 5
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Elevation in sAPP␣ was not found for children with mild autism in either study and may not be applicable to this population.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > LINKING SAPP WITH AUTISM
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These children expressed sAPP at 2 or more times the levels of children without autism and up to 4 times more than children with mild autism.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > LINKING SAPP WITH AUTISM
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, there was a trend toward higher levels of both sAPP␣ and total sAPP (sAPP is not a significant component of plasma total sAPP and was not measured) within children with autism, combined with a nonsignificant decrease in A-40.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > LINKING SAPP WITH AUTISM
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Macrocephaly has been one of the most widely replicated biological findings in autism, affecting up to 20% of all children with the condition 22 and confirmed by MRI volumetric studies.23”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > FEATURES OF AUTISM, AD, AND FXS Autism.
What the sources say
- Not matchedcites [22]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [23]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“When APP is processed alternatively via the nonamyloidogenic (␣-secretase) pathway, the secreted alpha form of APP (sAPP␣) is produced.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > Abstract
What the sources say
- Not matchedcites e1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“In this model, environmental agents epigenetically disturb gene regulation in a long-term manner, beginning at early developmental stages, but these perturbations might not have pathologic results until significantly later in life.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > ROLE OF GENE-ENVIRONMENT INTERACTION IN THE ETIOLOGY OF NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS
What the sources say
- Not matchedcites [44]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“These results point to an activity-dependent regulatory relationship between FMRP and APP mediated by mGluR5 signaling and to loss of this FMRP-based regulation in FXS, thereby providing a link between neuronal proteins associated with AD and FXS (unpublished data, 2011).6,13,43”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > The relationship of APP to FMRP is mediated by mGluR.
What the sources say
- Not matchedcites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [13]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [43]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“In mice, sAPP␣ has been shown to increase neurite outgrowth and memory and protect against multiple insults.11”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > Abstract
What the sources say
- Not matchedcites [11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“mGluR induce activity-dependent protein synthesis by activating several pathways including the PI3K/mTOR pathway, e35,e36 which is a FMRPdependent pathway.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > RELATIONSHIPS AMONG NEURONAL PRO-TEINS IN AUTISM, AD, AND FXS
What the sources say
- Not matchedcites e35
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites e36
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Studies of children with FXS have shown macrocephaly 4 and derangement of white matter frontal-striatal pathways.32”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > FXS.
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [32]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Autism, FXS, and AD share uncertain etiologies, with opaque relationships between genes and the environment consistent with the recently proposed latent earlylife associated regulation (LEARn) model, positing latent changes in expression of specific genes initially primed at the developmental stage of life.44”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > ROLE OF GENE-ENVIRONMENT INTERACTION IN THE ETIOLOGY OF NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS
What the sources say
- Not matchedcites [44]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In FXS, where FMRPdependent translational repression of APP is absent, high basal levels of APP and elimination of activitydependent regulation of APP levels would be expected.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > The relationship of APP to FMRP is mediated by mGluR.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Specifically, we postulate that high levels of sAPP␣ may contribute to macrocephaly, observed in both FXS and autism, through its associated neurotrophic activity.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > LINKING SAPP WITH AUTISM
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
- Rests on an assumption: Plasma sAPPα levels reflect brain sAPPα levels or activity relevant to brain overgrowth in autism and FXS.
In the paper
“Activation of metabotropic glutamate receptor 5 (mGluR5) releases FMRP-mediated translation repression and results in protein synthesis-dependent LTD.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > RELATIONSHIPS AMONG NEURONAL PRO-TEINS IN AUTISM, AD, AND FXS
What the sources say
- Not matchedcites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This activity of sAPP␣ may be partially mediated by interactions with adhesion modulators, such as -catenin, thereby altering adhesion and migration of cortical neurons and promoting overgrowth.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > LINKING SAPP WITH AUTISM
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
- Rests on an assumption: Cell adhesion suppresses brain growth, while abnormalities in adhesion promote growth or contribute to aberrant growth.
In the paper
“Specifically, FMRP inhibits APP translation under basal conditions, but when mGluR5 receptors are activated, this inhibitory effect is released.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > The relationship of APP to FMRP is mediated by mGluR.
What the sources say
- Not matchedcites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“APP is the parental molecule of neurotoxic amyloid- peptide (A), produced by amyloidogenic processing of APP and secreted in excess in AD. e1”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > Abstract
What the sources say
- Not matchedcites e1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Fmr1-knockout mice show reduced LTP in cortex and amygdala e28-e30 and exaggerated mGluRdependent LTD in hippocampus and cerebellum.e31-e34”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > RELATIONSHIPS AMONG NEURONAL PRO-TEINS IN AUTISM, AD, AND FXS
What the sources say
- Not matchedcites e28-e30
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites e31-e34
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > Abstract
What the sources say
- Not matchedcites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Some of the known functions of APP in these processes include promotion of proliferation, cell-cell adhesion and migration, 10 and synaptogenesis.33”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > RELATIONSHIPS AMONG NEURONAL PRO-TEINS IN AUTISM, AD, AND FXS
What the sources say
- Not matchedcites [10]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [33]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The finding of exaggerated mGluR-LTD in the absence of FMRP suggests that LTD becomes uncoupled from mGluR5 activation and persists independent of FMRP-dependent new protein synthesis.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > RELATIONSHIPS AMONG NEURONAL PRO-TEINS IN AUTISM, AD, AND FXS
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This could result in CNS neural overgrowth and leads to the symptoms of fragile X syndrome (FXS) or autism.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > ROLE OF GENE-ENVIRONMENT INTERACTION IN THE ETIOLOGY OF NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: APP has been implicated in neurogenesis, which may set the stage for later prenatal to early postnatal overproliferation of neurons.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When FMRP is eliminated or diminished, translation of amyloid- (A) precursor protein (APP) mRNA is disinhibited resulting in elevated basal levels of APP protein and the elimination of activity-dependent dynamic APP production.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > ROLE OF GENE-ENVIRONMENT INTERACTION IN THE ETIOLOGY OF NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These wide-spectrum changes in APP processing modulate protein product levels in a direction that would be beneficial in both disorders according to our model and could partially explain the observed salutary effect of memantine in both disorders, aside from classic NMDAR antagonism.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > SUMMARY, POSSIBLE DRUG TARGETS, AND FUTURE PERSPECTIVES
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Plasma sAPPα levels reflect brain sAPPα levels or activity relevant to brain overgrowth in autism and FXS.
“We have reported high levels of total sAPP (including sAPP␣) in plasma of a small sample of young children with severe autism and aggression.13”
The paper relies on this without support.
Cell adhesion suppresses brain growth, while abnormalities in adhesion promote growth or contribute to aberrant growth.
“Cell adhesion suppresses brain growth, while abnormalities in adhesion promote growth or contribute to aberrant growth.”
The paper relies on this without support.
Findings from mouse models and cell culture about APP, FMRP, and mGluR5 apply to human autism, FXS, and AD.
“In mice, sAPP␣ has been shown to increase neurite outgrowth and memory and protect against multiple insults.11”
“Fmr1-knockout mice show reduced LTP in cortex and amygdala e28-e30 and exaggerated mGluRdependent LTD in hippocampus and cerebellum.e31-e34”
The paper relies on this without support.
PTEN is a tumor suppressor that regulates cell cycle through its antagonistic actions on the PI3K/Akt/mTOR pathway.
“PTEN is a tumor suppressor that regulates cell cycle through its antagonistic actions on the PI3K/Akt/mTOR pathway.”
The paper relies on this without support.
PTEN is a phosphatase that counteracts PI3K by dephosphorylating PIP3.
“Specifically, PTEN is a phosphatase that counteracts PI3K by dephoshorylating PIP3.”
The paper relies on this without support.
The mTOR signaling pathway is a central regulator of cell growth and proliferation that also regulates synaptic plasticity by modulating protein synthesis in an activity-dependent manner.
“The mTOR signaling pathway is a central regulator of cell growth and proliferation that also regulates synaptic plasticity by modulating protein synthesis in an activity-dependent manner.”
The paper relies on this without support.
In a healthy system, FMRP activity and mGluR5 activity work in homeostasis and neural proliferation is balanced, leading to a neurotypical condition.
“In a healthy system, FMRP activity and mGluR5 activity work in homeostasis and neural proliferation is balanced, leading to a neurotypical condition.”
The paper relies on this without support.
APP has been implicated in neurogenesis, which may set the stage for later prenatal to early postnatal overproliferation of neurons.
“APP has been implicated in neurogenesis, which may set the stage for later prenatal to early postnatal overproliferation of neurons.”
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.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > Abstract
“Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism.”
§ Autism, Alzheimer disease, and fragile X APP, FMRP, and mGluR5 are molecular links > SUMMARY, POSSIBLE DRUG TARGETS, AND FUTURE PERSPECTIVES
“mGluR5 activity in amyloid- (A) precursor protein (APP) mRNA translation is disinhibitory, so blocking mGluR5 is not likely to alter APP translation levels.”
Citations
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“Shared pathways between AD and Fragile X have been reported (Sokol et al., 2011).”
Glutamate, Glutamate Receptors, and Downstream Signaling Pathways
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“Treatment with glutamate receptor antagonists may help repress APP and serve as a therapeutic target for AD (Sokol et al., 2011).”
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“Alzheimer’s disease, Autism and Fragile X Syndrome are associated with a dysfunction in the processing of amyloid 3244 British Journal of Pharmacology (2018) 175 3239–3250 precursor protein (APP; Sokol et al., 2011).”
BackgroundEtiologies underlying sex differences in autism spectrum disorders
Schaafsma, S. M., & Pfaff, D. W. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.03.006 · Cited by 178
“Interestingly, amyloid-b precursor protein has been shown to be implicated in ASD (Sokol et al., 2011).”
Long, J. M., Maloney, B., Rogers, J. T., & Lahiri, D. K. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0266-3 · Cited by 141
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“Given the potential role for mGluR5 as a receptor for Aβ [17-20], we crossed mGluR5 knockout mice with APPswe/ PS1ΔE9 mice.”
BackgroundInfluentialHamilton, A., Vasefi, M., Tuin, C. V., McQuaid, R. J., Anisman, H., & Ferguson, S. S. G. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.077 · Cited by 135
“Ab oligomers and cellular prion protein (PrP C ) interact with mGluR5 to cause the release of Ca 2+ from intracellular stores, thus disrupting normal neuronal signaling and function (Renner et al., 2010; Sokol et al., 2011; Um et al., 2013; Haas et al., 2014).”
BackgroundAutism spectrum disorders: The quest for genetic syndromes
Zafeiriou, D., Ververi, A., Dafoulis, V., Kalyva, E., & Vargìami, E. (2013) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32152 · Cited by 116
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“The sigmoidal curves based on non-linear regression are also shown. mGluR5 has been shown to increase translation of APP mRNA (Westmark and Malter, 2007; Sokol et al., 2011; Westmark, 2013).”
BackgroundEmerging Roles for Long Non-Coding RNAs in Cancer and Neurological Disorders
Niland, C. N., Merry, C. R., & Khalil, A. M. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00025 · Cited by 103
“A common characteristic of AD is the formation of protein aggregates in neurons (Sokol et al., 2011).”
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“ALZHEIMER’S DISEASE AND GROUP 1 mGluR FUNCTION A possible link between FXS and AD has been proposed since FMR protein binds to the amyloid precursor protein (APP; Sokol et al., 2011), APP is overexpressed in the FMR1 KO mice brain (D’Agata et al.”
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“Among the 59 new autism genes discovered, 14 were associated with fragile X mental retardation protein (FMRP), which is associated with both FXS and regulation of the gene encoding mGluR5 (Sokol et al., 2011).”
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“It has been suggested that mGlu5 receptor activation stimulates the production of the secreted a form of the amyloid precursor protein (APP) (Sokol et al., 2011), an effect that is potentially beneficial in AD.”
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“Due to inaccessibility of brain tissue samples from living subjects, we have argued recently that the plasma levels of these “neuronal” proteins would reflect the change occurring in the CNS (Ray et al. 2011; Sokol et al. 2011).”
InfluentialSelf-citationMetabotropic Glutamate Receptors in Central Nervous System Diseases
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Neurodevelopmental Clues to Neurodegeneration
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Intellectual disability: dendritic anomalies and emerging genetic perspectives
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“New putative biomarkers, therapeutic strategies and targets are being tested (Alley et al., 2010; Bailey et al., 2011; Cogswell et al., 2008; Ray et al., 2011a) and are needed for successful intervention (Lahiri, 2011).”
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“Negative allosteric modulators (NAM) are antagonists at mGluR5 with implications for treatment of Fragile X syndrome (Michalon et al., 2012; Sokol et al., 2011), depression (Deschwanden et al.”
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“In addition, our findings provide new insights about the shared cognitive impairment in ASD and Scz and their transcriptome similarity with NDs 99,100 .”
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“Hyperactive mTOR and mGluR5 signaling are implicated in ASD and other psychiatric disorders [58, 59].”
BackgroundRegulation of senescence by microRNA biogenesis factors
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Self-citationAlterations in sleep, sleep spindle, and EEG power in mGluR5 knockout mice
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“Although the cause of neuronal degeneration is still unknown, experimental evidences illustrate a possible link between the increased Ab production and death of neurons [19–21].”
BackgroundThe human β-amyloid precursor protein: biomolecular and epigenetic aspects
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“These authors speculated that overproduction of APPsα may contribute to the state of brain overgrowth implicated in autism and FXS.”
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“Post mortem brain studies from individuals with autism have documented abnormalities in the cholinergic system and a connection between Alzheimer’s disease and autism has been proposed by many researchers [53,54].”
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Fragile X and APP: a Decade in Review, a Vision for the Future
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A common molecular signature in ASD gene expression: following Root 66 to autism
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FMRP-Driven Neuropathology in Autistic Spectrum Disorder and Alzheimer's disease: A Losing Game
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“…RNA binding protein 309550 Santoro et al. (2011), Schaeffer et al. (2001) APP Amyloid precursor protein Transmembrane protein/cell signaling 104760 Sokol et al. (2011) MMP9 Matrix metalloproteinase 9 Enzyme/collagenase/gelatinase 120361 Janusz et al. (2013) MAP1B Microtubule-associated protein 1B…”
BackgroundDifferential effects of protein phosphatases in the recycling of metabotropic glutamate receptor 5
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Metabotropic glutamate receptor 5 as a potential therapeutic target in Huntington’s disease
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“located at the synapse, APP is released from neurons in an activity-dependent manner; the activation of mGluR5 results in FMRP-mediated translation of APP, and under normal conditions this effect may be neuroprotective [90].”
BackgroundFragile X syndrome: An aging perspective
Schneider, A., Ligsay, A., & Hagerman, R. J. (2013) · Developmental Disabilities Research Reviews · doi:10.1002/ddrr.1129 · Cited by 23
“A recent study by Sokol et al. [ 2011] elucidated that mGluR activity releases FMRP from APP mRNA, thus freeing it for translation [Sokol et al., 2011].”
BackgroundFragile X mental retardation protein expression in Alzheimer’s disease
Renoux, A. J., Carducci, N. M., Ahmady, A. A., & Todd, P. K. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00360 · Cited by 23
Fragile X mental retardation protein: from autism to neurodegenerative disease
Wang, H. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00043 · Cited by 26
Duda, P., Wójcicka, O., Wiśniewski, J. R., & Rakus, D. (2018) · Aging · doi:10.18632/aging.101501 · Cited by 21
Global Cerebral and Regional Multimodal Neuroimaging Markers of the Neurobiology of Autism
Hasan, K. M., Walimuni, I. S., & Frye, R. E. (2012) · Journal of Child Neurology · doi:10.1177/0883073812452917 · Cited by 21
Bailey, A. R., Hou, H., Obregon, D. F., Tian, J., Zhu, Y., Zou, Q., Nikolic, W. V., Bengtson, M. A., Mori, T., Murphy, T. K., et al. (2011) · The FASEB Journal · doi:10.1096/fj.11-195438 · Cited by 22
Leveraging gene co-regulation to identify gene sets enriched for disease heritability
Siewert, K. M., Kim, S. S., Yao, D. W., Shi, H., & Price, A. L. (2022) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2022.01.005 · Cited by 21
Harvey, B. D., Siok, C. J., Kiss, T., Volfson, D., Grimwood, S., Shaffer, C. L., & Hajós, M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.06.020 · Cited by 21
Ortí, J. E. D. L. R., Moneti, C., Serrano-Ballesteros, P., Castellano, G., Bayona-Babiloni, R., Carriquí-Suárez, A. B., Motos-Muñoz, M., Proaño, B., & Benlloch, M. (2023) · Nutrients · doi:10.3390/nu15143265 · Cited by 18
Quantification of various APP-mRNA isoforms and epistasis in Lesch-Nyhan disease
Nguyen, K. V., & Nyhan, W. L. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.02.016 · Cited by 18
Analysis of peripheral amyloid precursor protein in Angelman Syndrome
Erickson, C. A., Wink, L. K., Bayon, B. L., Ray, B., Schaefer, T. L., Pedapati, E. V., & Lahiri, D. K. (2016) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37811 · Cited by 18
“In humans with idiopathic and FXS-associated ASD, we have shown that the glutamate and GABA modulator acamprosate reduces peripheral APP total and sAPPa levels with treatment.”
BackgroundInfluentialSelf-citationIscru, E., Goddyn, H., Ahmed, T., Callaerts‐Vegh, Z., D’Hooge, R., & Balschun, D. (2013) · Genes Brain & Behavior · doi:10.1111/gbb.12052 · Cited by 17
“…schizophrenia, Parkinson’s disease, fragile X syndrome, Lewy body and Alzheimer’s disease (Gross et al. 2012; Hopkins et al. 2009; Krystal et al. 2010; Lee et al. 1995; Luscher & Huber 2010; Niswender & Conn 2010; Osterweil et al. 2010; Price et al. 2010; Ribeiro et al. 2010; Sokol et al. 2011).”
BackgroundMockett, B. G., & Ryan, M. M. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.05.014 · Cited by 18
Nguyen, K. V. (2015) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257770.2015.1071844 · Cited by 15
“Treatment with metabotropic glutamate receptor 5 (mGluR5) antagonists may help repress APP-mRNA translation and reduce secretion of APPsα in autism and FXS has been also suggested.[44] In any way, an accurate quantification of various APP-mRNA isoforms in brain tissues for detection of initial pathological changes or…”
BackgroundCarter, C. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.03.007 · Cited by 15
“2008, 2013) and that dampening sAPPα production with metabotropic glutamate receptor agonists may be effective in these conditions (Sokol et al., 2011).”
Frederikse, P. H., Nandanoor, A., & Kasinathan, C. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1702-2 · Cited by 14
“FMRP decreases with aging in the brain and was associated with Alzheimer’s disease (AD) [2, 3].”
BackgroundDementia in Rare Genetic Neurodevelopmental Disorders
Kwetsie, H., van Schaijk, M., van der Lee, S. J., Festen, D. A. M., ten Hoopen, L. W., van Haelst, M. M., Coesmans, M., van den Berg, E., de Wit, M. Y., Pijnenburg, Y. A. L., et al. (2024) · Neurology · doi:10.1212/wnl.0000000000209413 · Cited by 13
Rahman, M. S., Yang, J., Luan, Y., Qiu, Z., Zhang, J., Lü, H., Chen, X., & Liu, Y. U. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03006-1 · Cited by 14
Esterlis, I., DeBonee, S., Cool, R., Holmes, S. E., Baldassarri, S. R., Maruff, P. T., Pietrzak, R. H., & Davis, M. T. (2022) · Chronic Stress · doi:10.1177/24705470221105804 · Cited by 14
Axonal and presynaptic FMRP: Localization, signal, and functional implications
Wang, X., Sela‐Donenfeld, D., & Wang, Y. (2023) · Hearing Research · doi:10.1016/j.heares.2023.108720 · Cited by 13
Sokol, D. K., & Lahiri, D. K. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1201723 · Cited by 11
Self-citationDoes Bisphenol A (BPA) Exposure Cause Human Diseases?
Stein, T. P. (2024) · Biomedicines · doi:10.3390/biomedicines12122678 · Cited by 15
Fragile X gene expansions are not associated with dementia
Hall, D. A., Bennett, D. A., Filley, C. M., Shah, R. C., Kluger, B. M., Ouyang, B., & Berry‐Kravis, E. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.04.027 · Cited by 11
“There is an activity-dependent regulatory relationship between the fragile X mental retardation protein (FMRP) and amyloid precursor protein (APP), which when cleaved, is a major component of cerebral amyloid plaques found in AD (Sokol et al., 2011).”
BackgroundInitial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism
Erickson, C. A., Ray, B., Wink, L. K., Bayon, B. L., Pedapati, E. V., Shaffer, R. C., Schaefer, T. L., & Lahiri, D. K. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.09.003 · Cited by 10
“In this context, we have previously reported higher levels of secreted amyloid-β precursor protein-alpha form (sAPPα) and lower levels of potentially toxic amyloid-β (Aβ) peptide in plasma and brain tissue of children with severe autism (Sokol et al., 2006; Sokol et al., 2011; Lahiri et al., 2013).”
Self-citationSpecial Issue: Alzheimer’s disease
Nguyen, K. V. (2018) · AIMS neuroscience · doi:10.3934/neuroscience.2018.1.74 · Cited by 10
Zhang, Q., Liu, J., Liu, H., Ao, L., Yang, X., & Chen, D. (2024) · Scientific Reports · doi:10.1038/s41598-024-54541-8 · Cited by 9
Nagel, J., Greco, S., Parsons, C. G., Flik, G., Tober, C., Klein, K.-U., & Danysz, W. (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2015.01.004 · Cited by 9
Capkova, Z., Čapková, P., Srovnal, J., Štaffová, K., Becvarova, V., Trková, M., Adamová, K., Santavá, A., Curtisová, V., Hajdúch, M., et al. (2019) · PeerJ · doi:10.7717/peerj.7979 · Cited by 11
“, 2017) together with other neuropsychiatric disorders such as schizophrenia, Alzheimer’s disease, Parkinson’s disease, and others (Wolfe et al., 2017; Sokol et al., 2011; Catalá-López et al., 2014).”
BackgroundRibeiro, F. C., Cozachenco, D., Parkhill, M., Rodrigue, B., Borges, C., Lacaille, J., Nader, K., Felice, F. G. D., Lourenco, M. V., Aguilar‐Valles, A., et al. (2025) · Aging Cell · doi:10.1111/acel.70315 · Cited by 8
Chen, H., Qiao, D., Wang, C., Zhang, B., Wang, Z., Tang, L., Wang, Y., Zhang, R., Zhang, Y., Song, L., et al. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.872347 · Cited by 8
Wu, J., Xu, J. J., Naguib, M., & Bie, B. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03161-2 · Cited by 8
Lahiri, D. K., Maloney, B., Rogers, J. T., & Ge, Y. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-68 · Cited by 7
“protein, among its non-pathological functions, is active in the “neuronal pruning” stage of brain development, wherein neurons in the early brain are selectively removed after rapid proliferation [111].”
BackgroundSelf-citationDiverse Functions and Mechanisms of Mammalian Long Noncoding RNAs
Merry, C. R., Niland, C. N., & Khalil, A. M. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1369-5_1 · Cited by 9
Kaar, A., Weir, M. P., & Rae, M. G. (2024) · Neuroscience Letters · doi:10.1016/j.neulet.2024.137664 · Cited by 8
“Notably, with regard to the current study, aberrant I-mGluR-mediated calcium signaling is linked to the stimulation of amyloidogenic metabolism [17,48,49,53,85,108,109] which, in turn, disrupts synaptic function [51,60,81,84,99] in animal models of AD [37,78,85,99].”
Background
Metadata
- Authors
- Sokol, D. K., Maloney, B., Long, J. M., Ray, B., & Lahiri, D. K.
- Affiliations
- Indiana University Indianapolis (US)
- Venue
- Neurology
- Published
- 2011-04-12
- Volume
- 76
- Issue
- 15
- Pages
- 1344-1352
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3090060
- OpenAlex
- W2042211936
- Cited by
- 141
- References
- 58
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 7 · 2023: 4 · 2022: 10 · 2021: 8 · 2020: 7 · 2019: 11 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 10 · 2014: 12 · 2013: 17 · 2012: 16
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- Alzheimer's Association (AG18379)
- National Institutes of Health (AG18379)
- National Institute on Aging (R01 AG018379, AG 18379, R01AG018884, AG18884)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- autism spectrum disorder, Alzheimer's disease, fragile X syndrome, amyloid precursor protein, sAPPα, FMRP, metabotropic glutamate receptor 5, amyloid-beta, intellectual disability, dendritic spines, brain overgrowth, mGluR antagonists, plasma biomarkers
- MeSH terms
- Alzheimer Disease, Autistic Disorder, Fragile X Syndrome, Humans, Amyloid beta-Protein Precursor, Receptors, Metabotropic Glutamate, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1, Receptor, Metabotropic Glutamate 5
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