Normal cognition in transgenic BRI2-Aβ mice
Open accessAbstract
Background: Recent research in Alzheimer’s disease (AD) field has been focused on the potential role of the amyloid-β protein that is derived from the transmembrane amyloid precursor protein (APP) in directly mediating cognitive impairment in AD. Transgenic mouse models overexpressing APP develop robust AD-like amyloid pathology in the brain and show various levels of cognitive decline. In the present study, we examined the cognition of the BRI2-Aβ transgenic mouse model in which secreted extracellular Aβ1-40, Aβ1-42 or both Aβ1-40/Aβ1-42 peptides are generated from the BRI-Aβ fusion proteins encoded by the transgenes. BRI2-Aβ mice produce high levels of Aβ peptides and BRI2-Aβ1-42 mice develop amyloid pathology that is similar to the pathology observed in mutant human APP transgenic models. Results: Using established behavioral tests that reveal deficits in APP transgenic models, BRI2-Aβ1-42 mice showed completely intact cognitive performance at ages both pre and post amyloid plaque formation. BRI2-Aβ mice producing Aβ1-40 or both peptides were also cognitively intact. Conclusions: These data indicate that high levels of Aβ1-40 or Aβ1-42, or both produced in the absence of APP overexpression do not reproduce memory deficits observed in APP transgenic mouse models. This outcome is supportive of recent data suggesting that APP processing derivatives or the overexpression of full length APP may contribute to cognitive decline in APP transgenic mouse models. Alternatively, Aβ aggregates may impact cognition by a mechanism that is not fully recapitulated in these BRI2-Aβ mouse models.
AI snapshot
Written from the paper’s full text.
TL;DR
BRI2-Aβ transgenic mice producing high levels of Aβ1-40, Aβ1-42, or both without APP overexpression showed no cognitive deficits on a behavioral battery at ages before and after amyloid plaque formation. This suggests that Aβ accumulation alone may not reproduce the memory deficits seen in APP transgenic models.
Key findings
- BRI2-Aβ1-42 mice had completely intact cognition at 12 months, when Aβ1-42 deposition begins, and at 14–17 months, when robust forebrain plaques are present; genotype effects were nonsignificant across fear conditioning, open-field, rotarod, water maze, and conditioned taste aversion tests (Table 1; ω² ranged from 0 to 0.09).
- BRI2-Aβ1-40 and BRI2-Aβ1-40/Aβ1-42 mice were also cognitively intact; bitransgenic mice showed reduced but not absent Aβ deposition.
- At 17 months, BRI2-Aβ1-42 mice had amyloid plaque pathology and RIPA-soluble/insoluble Aβ levels comparable to 4-month-old APP CRND8 mice, an age when CRND8 mice showed reliable cognitive impairment in prior studies; higher-molecular-weight Aβ oligomeric species were present.
- No significant correlations were found between forebrain Aβ1-42 levels and any non-cognitive or cognitive behavioral measure in BRI2-Aβ1-42 mice.
Methods
- BRI2-Aβ mice expressing Aβ1-40, Aβ1-42, or both were generated via a BRI2 fusion strategy and maintained on a hybrid C57/B6//C3H background; non-transgenic littermates served as controls.
- Study 1 tested 72 mice at 12 months in fear conditioning. Study 2 tested 27 mice longitudinally at 14.2, 14.6, 15.1, 15.3, and 15.8 months in open-field, rotarod, visible-platform and spatial-reference water maze, and conditioned taste aversion; a separate naive cohort of 24 mice was tested in water maze at 17 months.
- Aβ pathology was assessed by histochemical staining, sandwich ELISA after RIPA/SDS/formic acid extraction, and Western blotting; behavior was analyzed with factorial ANOVA/RMANOVA using genotype and sex, omega squared effect size, t-tests, and Spearman correlations.
Limitations
- The authors state they cannot exclude the possibility that Aβ40 or other APP derivatives are required to trigger cognitive deficits, and that future testing of very old BRI2-Aβ1-40/BRI2-Aβ1-42 mice was precluded by an extensive premature death phenotype.
- The authors note that acute injection of synthetic Aβ may be more toxic than chronic developmental exposure and may not reflect the BRI2-Aβ model’s prolonged, physiological Aβ secretion.
- Evident from the text: cognitive testing was limited to ages up to 17 months, and the comparison to APP CRND8 cognitive impairment relies on prior studies rather than a concurrent APP transgenic control in the same behavioral battery.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
15 of 34 cited sources checked · 9 supported · 0 flagged · accuracy not yet measured
- Study design and conductcitation
The study characterized multiple memory systems of BRI2-Aβ mice to strengthen experimental and external validity and eliminate potential false negative results of cognitive evaluation.
“To strengthen experimental and external validity of our study and to eliminate potential false negative results of cognitive evaluation, which could be observed only in one test or even limited to specific experimental settings [33], we characterized multiple memory systems of BRI2-Aβ mice.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [33] Corcoran KA, Lu Y, Turner RS, Maren S: Overexpression of hAPPswe impairs rewarded alternation and contextual fear conditioning in a transgenic mouse model of Alzheimer's disease. Learn Mem. 2002, 9: 243-252. 10.1101/lm.51002. source
- Premisecitation
Previous studies demonstrated age-dependent decline of conditioned fear memory in APP CRND8 mice.
“In our previous studies, we also demonstrated age-dependent decline of conditioned fear memory in APP CRND8 mice [25].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] Hanna A, Iremonger K, Das P, Dickson D, Golde T, Janus C: Age-related increase in amyloid plaque burden is associated with impairment in conditioned fear memory in CRND8 mouse model of amyloidosis. Alzheim Res Ther. 2012, 4: 21-10.1186/alzrt124. source
- Interpretationreasoning
Interaction with testing environment or personnel cannot explain the discrepancy, since the cognitive tests in the present study were run by the same PI and assistant as previously published work on APP CRND8 mice.
“In addition, interaction with testing environment [38,39], or personnel cannot explain the discrepancy, since the cognitive tests in the present study were run by the same PI (CJ) and assistant (AH) as our previously published work on APP CRND8 mice [10,25,34].”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [10] Hanna A, Horne P, Yager D, Eckman C, Eckman E, Janus C: Amyloid beta and impairment in multiple memory systems in older transgenic APP TgCRND8 mice. Genes Brain Behav. 2009, 8: 676-684. 10.1111/j.1601-183X.2009.00510.x. source
- cites [25] Hanna A, Iremonger K, Das P, Dickson D, Golde T, Janus C: Age-related increase in amyloid plaque burden is associated with impairment in conditioned fear memory in CRND8 mouse model of amyloidosis. Alzheim Res Ther. 2012, 4: 21-10.1186/alzrt124. source
- cites [34] Janus C, Welzl H, Hanna A, Lovasic L, Lane N, St George-Hyslop P, Westaway D: Impaired conditioned taste aversion learning in APP transgenic mice. Neurobiol Aging. 2004, 25: 1213-1219. 10.1016/j.neurobiolaging.2003.11.007. source
- Interpretationcitation
The reported behavioral outcomes in the rat model of virally-mediated BRI2-Aβ expression were not fully consistent with memory impairment.
“However, the reported behavioral outcomes were not fully consistent with memory impairment.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [58] Lawlor PA, Bland RJ, Das P, Price RW, Holloway V, Smithson L, Dicker BL, During MJ, Young D, Golde TE: Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Abeta levels. Mol Neurodegener. 2007, 2: 11-10.1186/1750-1326-2-11. source
- Interpretationcitation
The observed dissociation between Aβ accumulation in the brain of BRI2-Aβ1-42 mice and cognitive decline provides a novel research tool to investigate the formation of molecular assemblies and conformational changes, as well as contribution of additional factors which may lead to amyloid-β toxicity and consequently to memory decline.
“Overall, the observed dissociation between Aβ accumulation in the brain of BRI2-Aβ1-42 mice and cognitive decline provides a novel research tool to investigate the formation of molecular assemblies and conformational changes, as well as contribution of additional factors which may lead to amyloid-β toxicity and consequently to memory decline [59].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [59] Broersen K, Rousseau F, Schymkowitz J: The culprit behind amyloid beta peptide related neurotoxicity in Alzheimer's disease: oligomer size or conformation?. Alzheim Res Ther. 2010, 2: 12-10.1186/alzrt36. source
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
- Findingown data
BRI2-Aβ1-42 mice showed completely intact cognitive performance at ages both pre and post amyloid plaque formation.
“BRI2-Aβ1-42 mice showed completely intact cognitive performance at ages both pre and post amyloid plaque formation.”
Quote in the paperSubstantial claim - Findingown data
BRI2-Aβ mice producing Aβ1-40 or both peptides were also cognitively intact.
“BRI2-Aβ mice producing Aβ1-40 or both peptides were also cognitively intact.”
Quote in the paperSubstantial claim - Findingown data
In 17-month-old BRI2-Aβ1-42 mice, amyloid plaque pathology and RIPA soluble and insoluble Aβ levels were comparable to levels in APP CRND8 mice at age 4 months.
“In 17-month-old BRI2-Aβ1-42 mice, amyloid plaque pathology as well as RIPA soluble and insoluble Aβ levels were comparable to levels found in APP CRND8 mice at the age of 4 months (Figure 1E-F, and H)”
Quote in the paperSubstantial claim - Findingown data
Biochemical analysis revealed higher molecular weight Aβ oligomeric species in brain tissue of BRI2-Aβ1-42 mice.
“Biochemical analysis of Aβ revealed the presence of higher molecular weight Aβ oligomeric species in brain tissue of BRI2-Aβ1-42 mice (Figure 1G).”
Quote in the paperNot a substantial claim - Findingown data
Bitransgenic BRI2-Aβ1-40/BRI2-Aβ1-42 mice showed reduced but not absent Aβ deposition.
“Bitransgenic BRI2-Aβ1-40/BRI2-Aβ1-42 mice showed reduced Aβ, but not absent, deposition (Figure 1C and I)”
Quote in the paperSubstantial claim - Findingown data
At 14.6 months, there was no significant effect of genotype on rotarod performance.
“Locomotor balance and coordination of mice was evaluated in the rotarod test at the age of 14.6 months. There was no significant effect of the genotype (Table 1)”
Quote in the paperSubstantial claim - Findingown data
The effect size or amount of variance explained by genotype was either negligible to low, ranging from 0 to 0.09.
“This general conclusion is further substantiated by the fact that the effect size or amount of variance explained by the genotype was either negligible to low (ranging from 0 to 0.09, Table 1).”
Quote in the paperSubstantial claim - Findingown data
Neither BRI2-Aβ line showed compromised fear conditioned memory at the stage of early onset of Aβ pathology.
“Our present results showed conclusively that neither BRI2-Aβ line showed compromised fear conditioned memory at the stage of early onset of Aβ pathology”
Quote in the paperSubstantial claim - Findingown data
There were no significant correlations between Aβ1-42 levels in the BRI2-Aβ1-42 mice forebrain and any measure evaluating non-cognitive or cognitive behavior.
“Overall, there were no significant correlations between Aβ1-42 levels in the BRI2-Aβ1-42 mice forebrain and any measure evaluating non-cognitive or cognitive behavior obtained in the tests (data not shown).”
Quote in the paperSubstantial claim - Findingown data
At 14.2 months, both BRI2-Aβ lines and non-Tg mice showed comparable levels of exploration of the open-field arena and its inner part.
“The evaluation commenced at the age of 14.2 months and revealed that both BRI2-Aβ lines and non-Tg mice showed comparable levels of exploration of OF arena and its inner part (Figure 3A, Table 1).”
Quote in the paperSubstantial claim - Findingown data
Aged BRI2-Aβ1-42 mice developed Aβ1-42 plaques in the cortex and hippocampus.
“whereas aged BRI2-Aβ1-42 mice developed Aβ1-42 plaques in the cortex and hippocampus (Figure 1B)”
Quote in the paperSubstantial claim - Findingown data
At 15.1 months, all mice showed rapid improvement in reaching the cued platform in the visible platform water maze test.
“All mice showed rapid improvement in reaching the cued platform (F(2.42) = 40.8, p < 0.001, RMANOVA)”
Quote in the paperSubstantial claim - Findingown data
Mice of all three genotypes demonstrated comparable spatial memory in the probe trial at the end of training at 15.3 months.
“The mice of all three genotypes demonstrated comparable spatial memory evaluated in a probe trial at the end of training (Table 1, Figure 4C).”
Quote in the paperSubstantial claim - Findingown data
Overall amyloid plaque pathology was comparable between 17-month-old BRI2-Aβ1-42 mice and 4-month-old APP CRND8 mice.
“Although overall amyloid plaque pathology was comparable between 17 month old BRI2- Aβ1-42 mice and 4 month old APP CRND8 mice (Figure 1E, 1F)”
Quote in the paperSubstantial claim - Findingown data
At 15.8 months, all genotypes showed strong and comparable memory of the association between novel taste of saccharine and experimentally induced gastric nausea, significantly avoiding saccharine during the choice test on D2.
“The results revealed that all genotypes showed strong and comparable memory of the association between novel taste of saccharine and experimentally induced gastric nausea (Table 1), significantly avoiding the taste of saccharine during the choice test carried out on D2 after CS-US pairing (ps < 0.001, one-sample Student t-test with scores evaluated against 50% chance level, Figure 5A).”
Quote in the paperSubstantial claim - Findingcitation
BRI2-Aβ1-40 mice did not develop amyloid deposits.
“As previously reported, BRI2-Aβ1-40 mice did not develop amyloid deposits (Figure 1A)”
Quote in the paperSubstantial claim - Findingown data
In BRI2-Aβ1-42 mice, Aβ accumulation in the brain is dissociated from cognitive decline.
“Overall, the observed dissociation between Aβ accumulation in the brain of BRI2-Aβ1-42 mice and cognitive decline provides a novel research tool to investigate the formation of molecular assemblies and conformational changes, as well as contribution of additional factors which may lead to amyloid-β toxicity and consequently to memory decline [59].”
Quote in the paperSubstantial claim - Study design and conductown data
Extensive premature death in BRI2-Aβ1-40/Aβ1-42 bitransgenic mice precluded rigorous evaluation of cognition at old age.
“However, extensive premature death phenotype in the bitransgenic mice has precluded rigorous evaluation of cognition at old age.”
Quote in the paperSubstantial claim - Interpretationown data
The outcome is supportive of recent data suggesting that APP processing derivatives or the overexpression of full length APP may contribute to cognitive decline in APP transgenic mouse models.
“This outcome is supportive of recent data suggesting that APP processing derivatives or the overexpression of full length APP may contribute to cognitive decline in APP transgenic mouse models.”
Quote in the paperSubstantial claim - Study design and conductcitation
The chosen experimental paradigms were successfully used in the lab to demonstrate impairment in APP CRND8 mice.
“The chosen experimental paradigms were successfully used in our lab to demonstrate impairment in APP CRND8 mice, and focused on spatial learning and reference memory evaluated in WM test [9,10,13] and conditioned taste aversion, a form of Pavlovian associative learning, [34], in addition to the context and tone conditioned fear memory paradigm [25]”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [9] Chishti MA, Yang DS, Janus C, Phinney AL, Horne P, Pearson J, Strome R, Zuker N, Loukides J, French J: Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem. 2001, 276: 21562-21570. 10.1074/jbc.M100710200. source
- cites [10] Hanna A, Horne P, Yager D, Eckman C, Eckman E, Janus C: Amyloid beta and impairment in multiple memory systems in older transgenic APP TgCRND8 mice. Genes Brain Behav. 2009, 8: 676-684. 10.1111/j.1601-183X.2009.00510.x. source
- cites [13] Janus C, Pearson J, McLaurin J, Mathews PM, Jiang Y, Schmidt SD, Chishti MA, Horne P, Heslin D, French J: A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature. 2000, 408: 979-982. 10.1038/35050110. source
- Interpretationown data
High levels of Aβ1-40 or Aβ1-42, or both produced in the absence of APP overexpression do not reproduce memory deficits observed in APP transgenic mouse models.
“These data indicate that high levels of Aβ1-40 or Aβ1-42, or both produced in the absence of APP overexpression do not reproduce memory deficits observed in APP transgenic mouse models.”
Quote in the paperSubstantial claim - Interpretationcitation
The notion that Aβ aggregates are not sufficient to induce memory dysfunction in mice does not contradict studies showing that synthetic Aβ or Aβ aggregates injected into rodent brain may mediate memory formation.
“The notion that Aβ aggregates are not sufficient to induce memory dysfunction in mice does not contradict the results of the studies that show that synthetic Aβ or Aβ aggregates injected into rodent brain may mediate memory formation e.g. [28,57].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [28] Amaral FA, Lemos MT, Dong KE, Bittencourt MF, Caetano AL, Pesquero JB, Viel TA, Buck HS: Participation of kinin receptors on memory impairment after chronic infusion of human amyloid-beta 1–40 peptide in mice. Neuropeptides. 2010, 44: 93-97. 10.1016/j.npep.2009.10.006. source
- cites [57] O'Hare E, Scopes DI, Treherne JM, Monaghan J, Palmer PM, Amijee H, Kim EM: Novel anti-inflammatory compound SEN1176 alleviates behavioral deficits induced following bilateral intrahippocampal injection of aggregated amyloid-beta(1)(−)(4)(2). J Alzheimers Dis. 2011, 25: 219-229. source
- Interpretationown data
Chronic exposure to aggregated extracellular Aβ is not, by itself, sufficient to cause memory impairment in mice.
“Overall, our results suggest that chronic exposure to aggregated extracellular Aβ is not, by itself, sufficient to cause memory impairment in mice.”
Quote in the paperSubstantial claim - Interpretationreasoning
The present results point to possible roles of full length APP or other APP derivatives in mediating Aβ-associated toxicity in mouse models.
“Primarily, they point to possible roles of full length APP or other APP derivatives in mediating Aβ-associated toxicity in mouse models.”
Quote in the paperSubstantial claim - Premisecitation
Both BRI2-Aβ1-40 and BRI2-Aβ1-42 mice show the presence of the respective soluble Aβ peptides at age 3 months at levels about 2- to 3-fold higher than levels of Aβ in 3- to 6-month-old APP Tg2576 mice.
“Both BRI2-Aβ1-40 and BRI2-Aβ1-42 mice show the presence of the respective soluble Aβ peptides at the age of 3 months at levels ~2- to 3-fold higher than the levels of Aβ in 3- to 6-month-old APP Tg2576 mice.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P: Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron. 2005, 47: 191-199. 10.1016/j.neuron.2005.06.030. source
- Interpretationcitation
The discrepancy in cognitive profiles between BRI2-Aβ and APP transgenic mice cannot be easily attributed to mouse genetic background, since genetic background is comparable between BRI2-Aβ and CRND8 models.
“This discrepancy in cognitive profiles between BRI2-Aβ and APP transgenic mice, for example APP CRND8 model tested intensively in our laboratory, cannot be easily attributed to the mouse genetic background, which is known to modulate behavior [35-37], since genetic background is comparable between BRI2-Aβ and CRND8 models [7,9].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [7] McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P: Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron. 2005, 47: 191-199. 10.1016/j.neuron.2005.06.030. source
- cites [9] Chishti MA, Yang DS, Janus C, Phinney AL, Horne P, Pearson J, Strome R, Zuker N, Loukides J, French J: Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem. 2001, 276: 21562-21570. 10.1074/jbc.M100710200. source
- Interpretationreasoning
Acute interventions in the adult brain might be more toxic than chronic exposures to increasing levels of extracellular soluble or aggregated Aβ during development.
“Our current findings would parsimoniously suggest that such acute interventions in the adult brain might be more toxic, and might not reflect the effects of chronic exposures to increasing levels of extracellular soluble or aggregated Aβ in the brain during development, a process which models AD-like amyloid formation in more realistic developmental time frames.”
Quote in the paperSubstantial claim - Interpretationreasoning
Acute interventions in the adult brain might not reflect the effects of chronic exposures to increasing levels of extracellular soluble or aggregated Aβ in the brain during development.
“Our current findings would parsimoniously suggest that such acute interventions in the adult brain might be more toxic, and might not reflect the effects of chronic exposures to increasing levels of extracellular soluble or aggregated Aβ in the brain during development, a process which models AD-like amyloid formation in more realistic developmental time frames.”
Quote in the paperSubstantial claim - Interpretationreasoning
In our models, prolonged and more physiological secretion of Aβ with progressing Aβ aggregation and accumulation seems to replicate more realistically the progression of Aβ pathology in the brain during ontogeny and the neuronal response to Aβ lesions.
“In our models, the prolonged and more physiological secretion of Aβ with progressing Aβ aggregation and accumulation seem to replicate more realistically the progression of Aβ pathology in the brain during ontogeny and the neuronal response to Aβ lesions.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 10
- May combine two claims. 9
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe accumulation of β-secretase cleaved fragments of APP has been implicated as mediators of behavioral dysfunction.
“The accumulation of β-secretase cleaved fragments of APP has been implicated as mediators of behavioral dysfunction”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [54] Mitani Y, Yarimizu J, Saita K, Uchino H, Akashiba H, Shitaka Y, Ni K, Matsuoka N: Differential effects between gamma-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. J Neurosci. 2012, 32: 2037-2050. 10.1523/JNEUROSCI.4264-11.2012. source
- cites [55] Tamayev R, D'Adamio L: Inhibition of gamma-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia. Mol Neurodegener. 2012, 7: 19-10.1186/1750-1326-7-19. source
- cites [56] Lorenzo A, Yuan M, Zhang Z, Paganetti PA, Sturchler-Pierrat C, Staufenbiel M, Mautino J, Vigo FS, Sommer B, Yankner BA: Amyloid beta interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease. Nat Neurosci. 2000, 3: 460-464. 10.1038/74833. source
Classified as probably not a substantial claim.
PremisecitationEvaluations of APP transgenic mice in the fear conditioning test demonstrated clear memory impairments in the Tg2576 model at ages preceding Aβ deposition.
“These results are apparently in contrast with the evaluations of APP transgenic mice in fear conditioning test, which demonstrated clear memory impairments in Tg2576 model at ages preceding Aβ deposition [32].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [32] Dineley KT, Hogan D, Zhang WR, Taglialatela G: Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice. Neurobiol Learn Mem. 2007, 88: 217-224. 10.1016/j.nlm.2007.03.010. source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationMany APP transgenic mouse models develop relevant AD-related Aβ pathology and exhibit cognitive impairment within 6 to 12 months of age.
“Though many APP transgenic mouse models have been shown to develop relevant AD-related Aβ pathology and exhibit cognitive impairment within 6 to 12 months of age [2-4]”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [2] Janus C, Chishti MA, Westaway D: Transgenic mouse models of Alzheimer's disease. Biochim Biophys Acta. 2000, 1502: 63-75. 10.1016/S0925-4439(00)00033-8. source
Table 2 reports Aβ plaque deposition by 6–12 months in several APP transgenic lines, and §4.2 reports cognitive impairment in Tg2576 mice from about 10 months. But §4.2 says several lines had not been behaviorally tested and cautions that apparent learning deficits in others were confounded. The paper therefore does not establish that many lines exhibited both pathology and cognitive impairment within 6–12 months (page numbers unavailable in our copy). (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [3] Ashe KH: Mechanisms of memory loss in Abeta and tau mouse models. Biochem Soc Trans. 2005, 33: 591-594. source
- cites [4] Higgins GA, Jacobsen H: Transgenic mouse models of Alzheimer's disease: phenotype and application. Behav Pharmacol. 2003, 14: 419-438. source
Classified as probably not a substantial claim.
PremisecitationAccumulation of sAPPβ and/or β-CTF may affect long-term potentiation and memory acquisition in mouse models.
“For example, the accumulation of amino-terminal-soluble APPβ (sAPPβ) and/or β-carboxyl-terminal fragments (β-CTF) may affect long-term potentiation (LTP) [5] and memory acquisition in mouse models [6].”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [5] Deyts C, Vetrivel KS, Das S, Shepherd YM, Dupre DJ, Thinakaran G, Parent AT: Novel GalphaS-protein signaling associated with membrane-tethered amyloid precursor protein intracellular domain. J Neurosci. 2012, 32: 1714-1729. 10.1523/JNEUROSCI.5433-11.2012. source
The Discussion (page not provided) proposes that signaling from accumulated APP-CTF could regulate synaptic plasticity and memory formation, which supports the claim’s cautious wording about a possible effect. The Results examine neurite outgrowth in cells and cultured neurons, not memory acquisition in mouse models; the cited passages also do not establish an effect of sAPPβ. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [6] Tamayev R, Matsuda S, Arancio O, D'Adamio L: β- but not γ-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia. EMBO Mol Med. 2012, 4: 171-179. 10.1002/emmm.201100195. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrevious studies have shown that aggregated Aβ can interact with APP.
“and previous studies have shown that aggregated Aβ can interact with APP [54-56]”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [54] Mitani Y, Yarimizu J, Saita K, Uchino H, Akashiba H, Shitaka Y, Ni K, Matsuoka N: Differential effects between gamma-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. J Neurosci. 2012, 32: 2037-2050. 10.1523/JNEUROSCI.4264-11.2012. source
The Introduction says Aβ is produced by cleavage of APP, and the cultured-cell results examine how drugs affect APP processing and Aβ secretion. Neither passage addresses whether aggregated Aβ interacts with APP; searches for that interaction and for Aβ oligomers binding APP found no supporting passage in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured - cites [55] Tamayev R, D'Adamio L: Inhibition of gamma-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia. Mol Neurodegener. 2012, 7: 19-10.1186/1750-1326-7-19. source
The Background states that Aβ is derived from APP and that BRI2 binds APP, but it does not say that aggregated Aβ interacts with APP. Searches for aggregated Aβ binding or interacting with APP found no passage addressing that interaction in our copy. (LLM, conf=0.73)
Experimental — accuracy not yet measured - cites [56] Lorenzo A, Yuan M, Zhang Z, Paganetti PA, Sturchler-Pierrat C, Staufenbiel M, Mautino J, Vigo FS, Sommer B, Yankner BA: Amyloid beta interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease. Nat Neurosci. 2000, 3: 460-464. 10.1038/74833. source
Classified as probably not a substantial claim.
PremisecitationSelective expression of Aβ1-42 and Aβ1-40 in the brain using virally-mediated gene transfer of BRI2-Aβ fusion proteins modified behavior in a rat model.
“Interestingly, it has been reported that selective expression of Aβ1-42 and Aβ1-40 in the brain using virally-mediated gene transfer of BRI2-Aβ fusion proteins modified behavior in a rat model [58].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [58] Lawlor PA, Bland RJ, Das P, Price RW, Holloway V, Smithson L, Dicker BL, During MJ, Young D, Golde TE: Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Abeta levels. Mol Neurodegener. 2007, 2: 11-10.1186/1750-1326-2-11. source
May combine two claims.
InterpretationcitationThe apparent lack of a consistent trend in behavioral changes across behavioral tests in AAV-BRI2-Aβ1-42 rats and their apparently unimpaired spatial and short-term object recognition memories are consistent with the lack of cognitive impairment in BRI2-Aβ1-42 mice observed in the present study.
“The apparent lack of a consistent trend in behavioral changes across behavioral tests in AAV-BRI2-Aβ1-42 rats and apparently their unimpaired spatial and short-term object recognition memories [58] are consistent with the lack of cognitive impairment in BRI2-Aβ1-42 mice observed in the present study.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [58] Lawlor PA, Bland RJ, Das P, Price RW, Holloway V, Smithson L, Dicker BL, During MJ, Young D, Golde TE: Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Abeta levels. Mol Neurodegener. 2007, 2: 11-10.1186/1750-1326-2-11. source
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
May combine two claims.
Findingown dataStudy 1 demonstrated uncompromised hippocampus-dependent contextual fear memory and amygdala-dependent tone fear memory in all BRI2-Aβ lines tested at early stages of Aβ1-42 pathology in BRI2-Aβ1-42 mice.
“In conclusion, the results of Study 1 demonstrated an uncompromised hippocampus-dependent contextual fear memory, and amygdala-dependent tone fear memory in all BRI2-Aβ lines tested at the early stages of Aβ1-42 pathology in BRI2-Aβ1-42 mice.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAt 15.3 months, non-Tg, BRI2-Aβ1-40, and BRI2-Aβ1-42 mice showed significant improvement in search paths for the submerged escape platform during training, with no significant effect of genotype.
“The results revealed that non-Tg, BRI2-Aβ1-40, and BRI2-Aβ1-42 mice showed a significant improvement in their search paths for the submerged escape platform during training (F(4,84) = 10.8, p < 0.001, RMANOVA, Figure 4A), with no significant effect of the genotype (Table 1)”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn a separate cohort of naïve 17-month-old mice, both non-Tg and BRI2-Aβ1-42 mice showed significant improvement in search path during training, with no significant differences between genotypes.
“The results revealed that similarly to the first WM test, both non-Tg and BRI2-Aβ1-42 mice showed a significant improvement in their search path during training (F(4,76) = 5.8, p < 0.001, RMANOVA, Figure 4D), with no significant differences between the genotypes (Table 1) or interaction effects.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe presence of aggregated extracellular Aβ42 species along with concurrent overt Aβ42 amyloid plaque deposition at later ages did not affect motivation to explore the novel environment of the open-field arena, motor coordination, or swimming ability.
“Our results also indicate that the presence of aggregated extracellular Aβ42 species along with concurrent overt Aβ42 amyloid plaque deposition at later ages did not affect motivation to explore novel environment of the open-field arena, their motor coordination, or swimming ability.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAt 12 months, comparison between non-Tg and the three BRI2-Aβ lines did not reveal significant genotype differences in initial exploration of the training chamber or in freezing rates during contextual and tone memory tests.
“The comparison between non-transgenic (non-Tg) and the three BRI2-Aβ (BRI2-Aβ1-40, BRI2-Aβ1-42, and BRI2Aβ1-40/Aβ1-42) lines did not reveal significant genotype differences in the initial exploration of the training chamber (Table 1) or in freezing rates during contextual and tone memory tests (Figure 2, Table 1).”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationOnly BRI2-Aβ1-42 mice develop Aβ amyloid pathology in the brain at age 12 months with robust compact Aβ plaques in the hippocampus at 14 months.
“However, only BRI2-Aβ1-42 mice develop Aβ amyloid pathology in the brain at the age of 12 months with robust compact Aβ plaques in the hippocampus at 14 months [7].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P: Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron. 2005, 47: 191-199. 10.1016/j.neuron.2005.06.030. source
Probably not a substantial claim: may not pass S4 (based).
Premisenone givenOverexpression of full-length human APP in transgenic mice generates multiple biologically active APP proteolytic fragments potentially capable of altering behaviour.
“The overexpression of full-length human APP in transgenic mice generates multiple biologically active APP proteolytic fragments, potentially capable of altering behaviour.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationThe tests in the battery were administered from least to most invasive to minimize affecting behavior by prior test history.
“The tests in the battery were administered in the above listed order, from least to most invasive [61], to minimize affecting behavior by prior test history.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [61] McIlwain KL, Merriweather MY, Yuva-Paylor LA, Paylor R: The use of behavioral test batteries: effects of training history. Physiol Behav. 2001, 73: 705-717. 10.1016/S0031-9384(01)00528-5. source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationOmega squared estimates the proportion of systematic variance in the population instead of the sample, thus allowing better generalization of results, and it is relatively independent of sample size.
“Omega squared estimates the proportion of systematic variance in the population instead of the sample [66], thus allowing better generalization of results, and it is relatively independent of sample size [67,68].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [66] Tabachnick BG, Fidell LS: Using Multivariate Statistics. 1989, New York: Harper Collins Publishers Inc, 2
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [67] Levine TR, Hullett CR: Eta squared, partial eta squared, and misreporting of effect size in communication research. Hum Commun Res. 2002, 28: 612-625. 10.1111/j.1468-2958.2002.tb00828.x. source
- cites [68] Cohen J: Statistical Power Analysis for the Behavioural Sciences. 1988, Hillsdale, New Jersey: Lawrence Erlbaum Associates Inc
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataOne male in the BRI2-Aβ1-42 group died before the onset of the CTA test, reducing the sample size of this group to 8 mice.
“One male in BRI2-Aβ1-42 group died before the onset of CTA test, reducing the sample size of this group to 8 mice.”
Quote in the paperNot a substantial claim
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.
- ConsistentF(1, 64) = 4.8reported p < .05 · recomputed p = .032
“F(1,64) = 4.8, p < .05”
- ConsistentF(1, 21) = 5.5reported p < .05 · recomputed p = .029
“F(1,21) = 5.5, p < .05”
- ConsistentF(2, 48) = 7.3reported p < .01 · recomputed p = .002
“F(2,48) = 7.3, p < .01”
- ConsistentF(2, 42) = 38.9reported p < .001 · recomputed p < .001
“F(2,42) = 38.9, p < .001”
- ConsistentF(2, 21) = 2reported p = .2 · recomputed p = .160
“F(2,21) = 2.0, p = .2”
- ConsistentF(1, 21) = 0.1reported p = .8 · recomputed p = .755
“F(1,21) = 0.1, p = .8”
- ConsistentF(2, 21) = 0.2reported p = .8 · recomputed p = .820
“F(2,21) = 0.2, p = .8”
- ConsistentF(2, 24) = 2.3reported p = .1 · recomputed p = .122
“F(2,24) = 2.3, p = .1”
- ConsistentF(4, 84) = 10.8reported p < .001 · recomputed p < .001
“F(4,84) = 10.8, p < .001”
- ConsistentF(1, 21) = 10.1reported p < .01 · recomputed p = .005
“F(1,21) = 10.1, p < .01”
- ConsistentF(1, 21) = 2reported p = .17 · recomputed p = .172
“F(1,21) = 2.0, p = .17”
- Consistentt(25) = 1.4reported p = .2 · recomputed p = .174
“t(25) = 1.4, p = .2”
- ConsistentF(4, 76) = 5.8reported p < .001 · recomputed p < .001
“F(4,76) = 5.8, p < .001”
- Consistentt(10) = 2.6reported p = .026 · recomputed p = .026
“t(10) = 2.6, p = .026”
- Consistentt(12) = 2.5reported p = .027 · recomputed p = .028
“t(12) = 2.5, p = .027”
- ConsistentF(1, 35) = 14.1reported p < .01 · recomputed p < .001
“F(1,35) = 14.1, p < .01”
- ConsistentF(1, 35) = 4.8reported p < .05 · recomputed p = .035
“F(1,35) = 4.8, p < .05”
- ConsistentF(1, 35) = 11.7reported p < .01 · recomputed p = .002
“F(1,35) = 11.7, p < .01”
- Consistentt(22) = 2.2reported p < .05 · recomputed p = .039
“t(22) = 2.2, p < .05”
- Consistentt(19) = 2.8reported p < .02 · recomputed p = .011
“t(19) = 2.8, p < .02”
- ConsistentF(2, 40) = 2reported p = .16 · recomputed p = .149
“F(2,40) = 2.0, p = .16”
- ConsistentF(1, 30) = 1reported p = .34 · recomputed p = .325
“F(1,30) = 1.0, p = .34”
- ConsistentF(5, 30) = 1.3reported p = .31 · recomputed p = .290
“F(5,30) = 1.3, p = .31”
- ConsistentF(2, 20) = 1.3reported p = .3 · recomputed p = .295
“F(2,20) = 1.3, p = .30”
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.
Non-Tg probe-trial degrees of freedom exceed the stated group size
MinorThe methods specify 12 non-Tg mice in the 17-month-old cohort, but the reported one-sample test for that group has 12 degrees of freedom, which requires 13 observations.
“t(12) = 2.5, p = 0.027, comparison against 25% chance level for BRI2-Aβ1-42 and non-Tg respectively”
“cohort 2, of 24 mice (12(5m:7f) and 12(6m:6f) for non-Tg and BRI2-Aβ1-42 respectively) at the age of 17 months”
Conflicting ages for the open-field test
MinorThe results and methods place the open-field test at 14.2 months, but the Figure 3 caption places it at 14.4 months.
“The evaluation commenced at the age of 14.2 months and revealed that both BRI2-Aβ lines and non-Tg mice showed comparable levels of exploration of OF arena and its inner part”
“(A) The proportion of the exploration of center of the arena to total exploration path during the open-field test carried out at the age of 14.4 months.”
Cites
Tabachnick, B. G., & Fidell, L. S. (1983) · Cited by 79,888 · see citing works
Genetics of Mouse Behavior: Interactions with Laboratory Environment
Crabbe, J. C., Wahlsten, D., & Dudek, B. C. (1999) · Science · doi:10.1126/science.284.5420.1670 · Cited by 1,666 · see citing works
Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., et al. (2000) · Nature · doi:10.1038/35050110 · Cited by 1,431 · see citing works
Self-citationThe lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning
LeDoux, J., Cicchetti, P., Xagoraris, A., & Romanski, L. (1990) · The Journal of Neuroscience · doi:10.1523/jneurosci.10-04-01062.1990 · Cited by 1,167 · see citing works
Crouching as an index of fear.
Blanchard, R. J., & Blanchard, D. C. (1969) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0026779 · Cited by 1,077 · see citing works
Eta Squared, Partial Eta Squared, and Misreporting of Effect Size in Communication Research
Levine, T. R., & Hullett, C. R. (2002) · Human Communication Research · doi:10.1111/j.1468-2958.2002.tb00828.x · Cited by 998 · see citing works
Chishti, M. A., Yang, D.-S., Janus, C., Phinney, A. L., Horne, P., Pearson, J., Strome, R., Zuker, N., Loukides, J., French, J., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100710200 · Cited by 955 · see citing works
Self-citationSpatial learning with a minislab in the dorsal hippocampus.
Moser, M., Moser, E. I., Forrest, E., Andersen, P. N., & Morris, R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.21.9697 · Cited by 902 · see citing works
Taming anxiety in laboratory mice
Hurst, J. L., & West, R. S. (2010) · Nature Methods · doi:10.1038/nmeth.1500 · Cited by 599 · see citing works
The quantitative measurement of motor inco-ordination in naive mice using an accelerating rotarod
Jones, B. J., & Roberts, D. J. (1968) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1968.tb09743.x · Cited by 583 · see citing works
The use of behavioral test batteries: Effects of training history
McIlwain, K. L., Merriweather, M. Y., Yuva-Paylor, L. A., & Paylor, R. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00528-5 · Cited by 579 · see citing works
Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice
McGowan, E., Pickford, F., Kim, J., Onstead, L., Eriksen, J., Yu, C., Skipper, L., Murphy, M. P., Beard, J., Das, P., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.030 · Cited by 565 · see citing works
Self-citationFactors governing one-trial contextual conditioning
Fanselow, M. S. (1990) · Animal Learning & Behavior · doi:10.3758/bf03205285 · Cited by 564 · see citing works
Jonasson, Z. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.10.006 · Cited by 498 · see citing works
Probing the biology of Alzheimer’s disease in mice
Ashe, K. H., & Zahs, K. R. (2010) · Neuron · doi:10.1016/j.neuron.2010.04.031 · Cited by 413 · see citing works
Morris, R., & Frey, U. (1997) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1997.0136 · Cited by 366 · see citing works
Aβ40 Inhibits Amyloid Deposition<i>In Vivo</i>
Kim, J., Onstead, L., Randle, S., Price, R., Smithson, L., Zwizinski, C., Dickson, D. W., Golde, T., & McGowan, E. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4849-06.2007 · Cited by 359 · cited 3× · see citing works
“[24], which demonstrated the anti-amyloidogenic propensity of Aβ1-40 with respect to at least early stage amyloid deposition.”
BackgroundResultSelf-citationOwen, E. H., Logue, S. F., Rasmussen, D. L., & Wehner, J. M. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00165-6 · Cited by 347 · see citing works
Transgenic mouse models of Alzheimer’s disease.
Elder, G. A., Gama Sosa, M. A., & De Gasperi, R. (2010) · Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine · doi:10.1002/msj.20159 · Cited by 336 · see citing works
Chakrabarty, P., Jansen‐West, K., Beccard, A., Ceballos‐Diaz, C., Levites, Y., Verbeeck, C., Zubair, A. C., Dickson, D., Golde, T. E., & Das, P. (2010) · The FASEB Journal · doi:10.1096/fj.09-141754 · Cited by 328 · see citing works
Self-citationAugmented Senile Plaque Load in Aged Female β-Amyloid Precursor Protein-Transgenic Mice
Callahan, M. J., Lipinski, W. J., Bian, F., Durham, R. A., Pack, A., & Walker, L. C. (2001) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64064-3 · Cited by 274 · see citing works
Lorenzo, A., Yuan, M., Zhang, Z., Paganetti, P. A., Sturchler-Pierrat, C., Staufenbiel, M., Mautino, J., Vigo, F. S., Sommer, B., & Yankner, B. A. (2000) · Nature Neuroscience · doi:10.1038/74833 · Cited by 258 · see citing works
Benice, T. S., Rizk, A., Kohama, S., Pfankuch, T., & Raber, J. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.08.029 · Cited by 254 · see citing works
On the construct validity of open-field measures.
Royce, J. R. (1977) · Psychological Bulletin · doi:10.1037/0033-2909.84.6.1098 · Cited by 247 · see citing works
From contextual fear to a dynamic view of memory systems
Fanselow, M. S. (2010) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2009.10.008 · Cited by 227 · see citing works
Conditioned taste aversion as a learning and memory paradigm
Welzl, H., D’Adamo, P., & Lipp, H.-P. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00302-3 · Cited by 220 · see citing works
Dineley, K. T., Xia, X., Bui, D., Sweatt, J. D., & Zheng, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200164200 · Cited by 212 · see citing works
Mitani, Y., Yarimizu, J., Saita, K., Uchino, H., Akashiba, H., Shitaka, Y., Ni, K., & Matsuoka, N. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4264-11.2012 · Cited by 203 · see citing works
Search Strategies Used byAPPTransgenic Mice During Navigation in the Morris Water MazePreprint
Janus, C. (2004) · Learning & Memory · doi:10.1101/lm.70104 · Cited by 194 · see citing works
Self-citationBroersen, K., Rousseau, F., & Schymkowitz, J. (2010) · Alzheimer's Research & Therapy · doi:10.1186/alzrt36 · Cited by 168 · see citing works
Dineley, K. T., Hogan, D., Zhang, W.-R., & Taglialatela, G. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.03.010 · Cited by 149 · see citing works
Transgenic mouse models of Alzheimer's disease: phenotype and application.
(2003) · PubMed · doi:10.1097/01.fbp.0000088420.18414.ff · Cited by 147 · see citing works
Plaques, Tangles, and Memory Loss in Mouse Models of Neurodegeneration
Eriksen, J. L., & Janus, C. G. (2007) · Behavior Genetics · doi:10.1007/s10519-006-9118-z · Cited by 146 · see citing works
Self-citationTamayev, R., Matsuda, S., Arancio, O., & D'Adamio, L. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201100195 · Cited by 142 · see citing works
Corcoran, K. A., Lu, Y., Turner, R. S., & Maren, S. (2002) · Learning & Memory · doi:10.1101/lm.51002 · Cited by 135 · see citing works
Sex difference in pathology and memory decline in rTg4510 mouse model of tauopathy
Yue, M., Hanna, A., Wilson, J., Roder, H. M., & Janus, C. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.04.006 · Cited by 125 · see citing works
Self-citationBerger-Sweeney, J. E., Arnold, A., Gabeau, D., & Mills, J. (1995) · Behavioral Neuroscience · doi:10.1037//0735-7044.109.5.859 · Cited by 113 · see citing works
Transgenic mouse models of Alzheimer’s disease
Janus, C., Chishti, M. A., & Westaway, D. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00033-8 · Cited by 101 · see citing works
Self-citationInbred mouse strain differences in the establishment of long-term fear memory
Balogh, S. A., & Wehner, J. M. (2003) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00279-6 · Cited by 97 · see citing works
Maynard, C. J., Cappai, R., Volitakis, I., Cherny, R. A., Masters, C. L., Li, Q., & Bush, A. I. (2006) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2006.02.010 · Cited by 96 · see citing works
Berger-Sweeney, J. E., Arnold, A., Gabeau, D., & Mills, J. (1995) · Behavioral Neuroscience · doi:10.1037/0735-7044.109.5.859 · Cited by 94 · see citing works
Spatial learning in transgenic mice expressing human presenilin 1 (PS1) transgenes
Janus, C., D’Amelio, S., Amitay, O. A., Chishti, M. A., Strome, R., Fraser, P., Carlson, G. A., Roder, J., George‐Hyslop, P. S., & Westaway, D. A. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00107-x · Cited by 88 · see citing works
Self-citationTamayev, R., & D’Adamio, L. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-19 · Cited by 81 · see citing works
Wolfer, D. P., & Lipp, H. (1992) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(92)90124-v · Cited by 73 · see citing works
Crabbe, J. C., Cotnam, C. J., Cameron, A. J., Schlumbohm, J. P., Rhodes, J. S., Metten, P., & Wahłsten, D. (2003) · Genes Brain & Behavior · doi:10.1034/j.1601-183x.2003.00023.x · Cited by 72 · see citing works
Lawlor, P. A., Bland, R. J., Das, P., Price, R. W., Holloway, V., Smithson, L., Dicker, B. L., During, M. J., Young, D., & Golde, T. E. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-11 · Cited by 67 · see citing works
Self-citationBehavioural and cellular effects of exogenous amyloid-β peptides in rodents.
Chambon, C., Wegener, N., Gravius, A., & Danysz, W. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.08.024 · Cited by 64 · see citing works
Axonal transport of British and Danish amyloid peptides via secretory vesicles
Choi, S., Vidal, R., Frangione, B., & Levy, E. (2003) · The FASEB Journal · doi:10.1096/fj.03-0730fje · Cited by 55 · see citing works
Impaired conditioned taste aversion learning in APP transgenic mice
Janus, C., Welzl, H., Hanna, A., Lovasic, L., Lane, N., St. George-Hyslop, P., & Westaway, D. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.11.007 · Cited by 51 · see citing works
Self-citationPortelius, E., Olsson, M., Brinkmalm, G., Rüetschi, U., Mattsson, N., Andréasson, U., Gobom, J., Brinkmalm, A., Hölttä, M., Blennow, K., et al. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120994 · Cited by 50 · see citing works
Reversible Pathologic and Cognitive Phenotypes in an Inducible Model of Alzheimer-Amyloidosis
Melnikova, T., Fromholt, S., Kim, H.-S., Lee, D., Xu, G. M., Price, A. R., Moore, B. D., Golde, T. E., Felsenstein, K. M., Savonenko, A. V., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4251-12.2013 · Cited by 48 · see citing works
Self-citationDeyts, C., Vetrivel, K. S., Das, S., Shepherd, Y. M., Dupré, D. J., Thinakaran, G., & Parent, A. T. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5433-11.2012 · Cited by 47 · see citing works
Malm, T., Ort, M., Tähtivaara, L., Jukarainen, N., Goldsteins, G., Puoliväli, J. T., Nurmi, A., Pussinen, R., Ahtoniemi, T., Miettinen, T.-K., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602896103 · Cited by 45 · see citing works
Mechanisms of memory loss in Aβ and tau mouse models
Ashe, K. H. (2005) · Biochemical Society Transactions · doi:10.1042/bst0330591 · Cited by 42 · see citing works
Behavioural profiling of a murine Charcot–Marie–Tooth disease type 1A model
Norreel, J.-C., Jamon, M., Riviere, G., et al. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01535.x · Cited by 41 · see citing works
Burgos‐Ramos, E., Puebla‐Jiménez, L., & Arilla, E. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.04.036 · Cited by 39 · see citing works
Hanna, A., Iremonger, K., Das, P., Dickson, D., Golde, T., & Janus, C. (2012) · Alzheimer's Research & Therapy · doi:10.1186/alzrt124 · Cited by 38 · see citing works
Self-citationSex-dependent cognitive phenotype of mice lacking mGluR8
Duvoisin, R. M., Villasana, L., Pfankuch, T., & Raber, J. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.01.006 · Cited by 33 · see citing works
Amaral, F. A., Lemos, M. T. R., Dong, K. E., Bittencourt, M. F. Q. P., Caetano, A. L., Pesquero, J. B., Viel, T. A., & Buck, H. S. (2010) · Neuropeptides · doi:10.1016/j.npep.2009.10.006 · Cited by 30 · see citing works
Mouse Models of Neurodegenerative Diseases: Criteria and General Methodology
Janus, C., & Welzl, H. (2009) · Methods in molecular biology · doi:10.1007/978-1-60761-058-8_19 · Cited by 27 · see citing works
Self-citationGonadotropins: A cohesive gender-based etiology of Alzheimer disease
Webber, K. M., Casadesús, G., Atwood, C., Bowen, R. L., Perry, G. L., & Smith, M. A. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.01.018 · Cited by 23 · see citing works
O'Hare, E., Scopes, D. I. C., Treherne, J. M., Monaghan, J., Palmer, P. M., Amijee, H., & Kim, E.-M. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-100044 · Cited by 22 · see citing works
Amyloid β and impairment in multiple memory systems in older transgenic APP TgCRND8 mice
Hanna, A., Horne, P., Yager, D., Eckman, C., Eckman, E., & Janus, C. (2009) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2009.00510.x · Cited by 20 · see citing works
Self-citationMouse Models for Drug Discovery
Proetzel, G., & Wiles, M. (2016) · Methods in Molecular Biology · doi:10.1007/978-1-4939-3661-8 · Cited by 20 · see citing works
Spatial Exploration in Transgenic Mice Expressing Human β-S100
Janus, C., Janus, M., & Roder, J. (1995) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1995.1044 · Cited by 18 · see citing works
Self-citationCognition and behavior in patients with Alzheimer's disease.
Ott, B. R. (2001) · PubMed · Cited by 17 · see citing works
Mouse Models for Drug Discovery
(2009) · Methods in molecular biology · doi:10.1007/978-1-60761-058-8 · Cited by 17 · see citing works
Imwalle, D. B., Adewale, H. B., Wills, A., Honda, S., Harada, N., & Rissman, E. F. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.06.005 · Cited by 15 · see citing works
Akimoto, H. (1961) · Brain and nerve · Cited by 13 · see citing works
To each her own: sexual dimorphisms in Alzheimer’s disease
Einstein, G. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00079-2 · Cited by 6 · see citing works
Slack, M., Hewitt, K. N., Ebling, F. J. P., & Cassaday, H. J. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.08.006 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Cohen J: Statistical Power Analysis for the Behavioural Sciences. 1988, Hillsdale, New Jersey: Lawrence Erlbaum Associates Inc
Cited by
Sorted by citations
A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965 · see citing works
Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
Kametani, F., & Hasegawa, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00025 · Cited by 836 · see citing works
The case for rejecting the amyloid cascade hypothesis
Herrup, K. (2015) · Nature Neuroscience · doi:10.1038/nn.4017 · Cited by 768 · see citing works
Three dimensions of the amyloid hypothesis: time, space and 'wingmen'
Musiek, E. S., & Holtzman, D. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4018 · Cited by 697 · see citing works
Amyloid-β-independent regulators of tau pathology in Alzheimer disease
van der Kant, R., Goldstein, L. S. B., & Ossenkoppele, R. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0240-3 · Cited by 580 · see citing works
Animal models of neurodegenerative diseases
Dawson, T. M., Golde, T. E., & Lagier-Tourenne, C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0236-8 · Cited by 576 · see citing works
Self-citationβ-amyloid Peptides and Amyloid Plaques in Alzheimer's Disease
Gouras, G. K., Olsson, T. T., & Hansson, O. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0313-y · Cited by 331 · see citing works
Amyloid β-protein oligomers and Alzheimer’s disease
Hayden, E. Y., & Teplow, D. B. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt226 · Cited by 276 · see citing works
Mitochondrial Dysfunction as a Driver of Cognitive Impairment in Alzheimer’s Disease
Sharma, C., Kim, S., Nam, Y., Jung, U. J., & Kim, S. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094850 · Cited by 241 · see citing works
Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer’s Disease Pathogenesis
Chakravorty, A., Jetto, C. T., & Manjithaya, R. R. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00311 · Cited by 219 · see citing works
Wang, Z., Jackson, R. J., Hong, W., Taylor, W. M., Corbett, G. T., Moreno, A. J., Liu, W., Li, S., Frosch, M. P., Slutsky, I., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2009-17.2017 · Cited by 154 · see citing works
Fasae, K. D., Abolaji, A. O., Faloye, T. R., Odunsi, A., Oyetayo, B. O., Enya, J. I., Rotimi, J. A., Akinyemi, R., Whitworth, A. J., & Aschner, M. (2021) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2021.126779 · Cited by 160 · see citing works
Kwak, S. S., Washicosky, K. J., Brand, E., von Maydell, D., Aronson, J., Kim, S., Capen, D. E., Cetinbas, M., Sadreyev, R., Ning, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15120-3 · Cited by 151 · see citing works
Current and emerging avenues for Alzheimer's disease drug targets
Loera‐Valencia, R., Cedazo-Mı́nguez, Á., Kenigsberg, P.-A., Page, G., Duarte, A. I., Giusti, P., Zusso, M., Robert, P. H., Frisoni, G. B., Cattaneo, A., et al. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12959 · Cited by 139 · see citing works
The Role of Mitochondrial Calcium Homeostasis in Alzheimer’s and Related Diseases
Ryan, K. C., Ashkavand, Z., & Norman, K. R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239153 · Cited by 107 · see citing works
Banik, A., Brown, R. E., Bamburg, J., Lahiri, D. K., Khurana, D., Friedland, R. P., Chen, W., Ding, Y., Mudher, A., Padjen, A. L., et al. (2015) · Journal of Alzheimer’s Disease · doi:10.3233/jad-150136 · Cited by 102 · see citing works
Janus, C., Flores, A. Y., Xu, G. M., & Borchelt, D. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.05.010 · Cited by 92 · see citing works
Self-citationShort Aβ peptides attenuate Aβ42 toxicity in vivo
Moore, B. D., Martin, J., de Mena, L., Sánchez, J., Cruz, P. E., Ceballos‐Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20170600 · Cited by 89 · see citing works
Self-citationCurrent and future treatment of amyloid diseases
Ankarcrona, M., Winblad, B. G., Monteiro, C., Fearns, C., Powers, E. T., Johansson, J., Westermark, G. T., Presto, J., Ericzon, B. ‐., & Kelly, J. W. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12506 · Cited by 87 · see citing works
The BRICHOS Domain, Amyloid Fibril Formation, and Their Relationship
Knight, S. D., Presto, J., Linse, S. S., & Johansson, J. (2013) · Biochemistry · doi:10.1021/bi400908x · Cited by 77 · see citing works
Johnson, E. C. B., Ho, K., Yu, G.-Q., Das, M., Sanchez, P. E., Djukic, B., Lopez, I., Yu, X., Gill, M., Zhang, W., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00393-5 · Cited by 73 · see citing works
An in vitro paradigm to assess potential anti-Aβ antibodies for Alzheimer’s disease
Jin, M., O’Nuallain, B., Hong, W., Boyd, J. D., Lagomarsino, V. N., O’Malley, T. T., Liu, W., Vanderburg, C. R., Frosch, M. P., Young‐Pearse, T. L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05068-w · Cited by 70 · see citing works
Mukhopadhyay, S., & Banerjee, D. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-215065 · Cited by 66 · see citing works
Secreted Chaperones in Neurodegeneration
Chaplot, K., Jarvela, T. S., & Lindberg, I. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00268 · Cited by 59 · see citing works
Oskarsson, M. E., Hermansson, E., Wang, Y., Welsh, N., Presto, J., Johansson, J., & Westermark, G. T. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1715951115 · Cited by 61 · see citing works
Targeting Alzheimer's disease with gene and cell therapies
Loera‐Valencia, R., Piras, A., Ismail, M.-A.-M., Manchanda, S., Eyjolfsdottir, H., Saido, T. C., Johansson, J., Eriksdotter, M., Winblad, B. G., & Nilsson, P. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12759 · Cited by 57 · see citing works
Poska, H., Haslbeck, M., Kurudenkandy, F. R., Hermansson, E., Chen, G., Kostallas, G., Abelein, A., Biverstål, H., Crux, S., Fisahn, A., et al. (2016) · Biochemical Journal · doi:10.1042/bcj20160277 · Cited by 58 · see citing works
Aging-Dependent Mitophagy Dysfunction in Alzheimer’s Disease
Song, M., Zhao, X., & Song, F. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02248-y · Cited by 56 · see citing works
Mably, A. J., Liu, W., Donald, J. M. M., Dodart, J., Bard, F., Lemere, C. A., O’Nuallain, B., & Walsh, D. M. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.07.008 · Cited by 52 · see citing works
The Post-amyloid Era in Alzheimer's Disease: Trust Your Gut Feeling
Osorio, C. P., Kanukuntla, T., Diaz, E. L., Jafri, N., Cummings, M., & Sfera, A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00143 · Cited by 49 · see citing works
The chaperone domain BRICHOS prevents amyloid β-peptide CNS toxicity in Drosophila melanogaster
Hermansson, E., Schultz, S. W., Crowther, D. C., Linse, S. S., Winblad, B. G., Westermark, G. T., Johansson, J., & Presto, J. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.014787 · Cited by 48 · see citing works
The biogenesis and biology of amyloid β oligomers in the brain
Ashe, K. H. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12084 · Cited by 45 · see citing works
Tambini, M. D., Yao, W., & D'Adamio, L. (2019) · Aging Cell · doi:10.1111/acel.13033 · Cited by 40 · see citing works
Specific Chaperones and Regulatory Domains in Control of Amyloid Formation
Landreh, M., Rising, A., Presto, J., Jörnvall, H., & Johansson, J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.653097 · Cited by 38 · see citing works
Buxbaum, J. N., & Johansson, J. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00119 · Cited by 37 · see citing works
Krstic, D., & Knuesel, I. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-62 · Cited by 36 · see citing works
The vexing complexity of the amyloidogenic pathway
Castro, M., Hadziselimovic, A., & Sanders, C. R. (2019) · Protein Science · doi:10.1002/pro.3606 · Cited by 36 · see citing works
The Brain–Heart Axis: Alzheimer’s, Diabetes, and Hypertension
Riching, A. S., Major, J. L., Londono, P., & Bagchi, R. A. (2019) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.9b00091 · Cited by 37 · see citing works
Hendrix, R. D., Ou, Y., Davis, J. E., Odle, A. K., Groves, T. R., Allen, A. R., Childs, G. V., & Barger, S. W. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.10.001 · Cited by 33 · see citing works
Application of CRISPR genetic screens to investigate neurological diseases
So, R. W. L., Chung, S., Lau, H. H. C., Watts, J. J., Gaudette, E. V., Al‐Azzawi, Z. A. M., Bishay, J., Lin, L. T., Joung, J., Wang, X., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0343-3 · Cited by 36 · see citing works
Interpreting Alzheimer’s disease clinical trials in light of the effects on amyloid-β
Toyn, J. H., & Ahlijanian, M. K. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt244 · Cited by 31 · see citing works
Synaptic Disruption by Soluble Oligomers in Patients with Alzheimer’s and Parkinson’s Disease
Gutierrez, B. A., & Limón, A. (2022) · Biomedicines · doi:10.3390/biomedicines10071743 · Cited by 31 · see citing works
Xu, G. M., Fromholt, S., Chakrabarty, P., Zhu, F., Liu, X., Pace, M. C., Koh, J., Golde, T. E., Levites, Y., Lewis, J. M., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00911-y · Cited by 28 · see citing works
Self-citationMounting evidence of FKBP12 implication in neurodegeneration
Caminati, G., & Procacci, P. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.284980 · Cited by 24 · see citing works
Takasugi, N., Komai, M., Kaneshiro, N., Ikeda, A., Kamikubo, Y., & Uehara, T. (2023) · Cells · doi:10.3390/cells12030454 · Cited by 26 · see citing works
Abelein, A., & Johansson, J. (2023) · RSC Medicinal Chemistry · doi:10.1039/d3md00040k · Cited by 25 · see citing works
Aβ-Degrading Proteases: Therapeutic Potential in Alzheimer Disease
Leissring, M. A. (2016) · CNS Drugs · doi:10.1007/s40263-016-0364-1 · Cited by 25 · see citing works
del Campo, M., & Teunissen, C. E. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131364 · Cited by 23 · see citing works
Tambaro, S., Galán-Acosta, L., Leppert, A., Chen, G., Biverstål, H., Presto, J., Nilsson, P., & Johansson, J. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004538 · Cited by 23 · see citing works
Yeast Model of Amyloid-β and Tau Aggregation in Alzheimer’s Disease
Moosavi, B., Mousavi, B., & Macreadie, I. G. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150173 · Cited by 19 · see citing works
Recent Mechanisms of Neurodegeneration and Photobiomodulation in the Context of Alzheimer’s Disease
Su, M., Nizamutdinov, D., Liu, H., & Huang, J. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119272 · Cited by 19 · see citing works
Dolfe, L., Winblad, B. G., Johansson, J., & Presto, J. (2015) · Biochemical Journal · doi:10.1042/bj20150920 · Cited by 17 · see citing works
Adebambo, K. F., & Ojoh, O. (2024) · International Journal of Alzheimer s Disease · doi:10.1155/2024/2988685 · Cited by 16 · see citing works
O-GlcNAcylation of Amyloid-β Protein Precursor by Insulin Signaling Reduces Amyloid-β Production
Kwon, O.-H., Cho, Y. Y., Kim, T., & Chung, S. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190060 · Cited by 16 · see citing works
Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice
Beglopoulos, V., Tulloch, J., Roe, A. D., Daumas, S., Ferrington, L., Watson, R., Fan, Z., Hyman, B. T., Kelly, P. A. T., Bard, F., et al. (2016) · Nature Communications · doi:10.1038/ncomms11761 · Cited by 16 · see citing works
BRI2 as an anti-Alzheimer gene
Matsuda, S., & Senda, T. (2018) · Medical Molecular Morphology · doi:10.1007/s00795-018-0191-1 · Cited by 13 · see citing works
Crnich, E., Lullo, R., Tabaka, A. L., Havens, M. A., & Kissel, D. S. (2021) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2021.111493 · Cited by 14 · see citing works
Research models to study lewy body dementia
Boschen, S. L., Mukerjee, A. A., Faroqi, A. H., Rabichow, B. E., & Fryer, J. D. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00837-w · Cited by 15 · see citing works
Wang, K., & Zhang, W. (2021) · Synapse · doi:10.1002/syn.22196 · Cited by 10 · see citing works
Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease
Tyler, S. E. B., & Tyler, L. D. K. (2022) · Natural Products and Bioprospecting · doi:10.1007/s13659-022-00354-z · Cited by 10 · see citing works
Impairment of visual cortical plasticity by amyloid-beta species
William, C. M., Stern, M., Pei, X., Saqran, L., Ramani, M. D., Frosch, M. P., & Hyman, B. T. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105344 · Cited by 8 · see citing works
D'adamio, L. (2023) · EMBO Molecular Medicine · doi:10.15252/emmm.202318479 · Cited by 6 · see citing works
Miotto, E. C., Brucki, S. M. D., Cerqueira, C. T., Bazán, P. R., Silva, G. A. A., Martin, M. D. G. M., Squarzoni, P., Faria, D. D. P., Coutinho, A. M., Buchpiguel, C. A., et al. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220100 · Cited by 6 · see citing works
Aβ degradation—the inside story
Leissring, M. A. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00229 · Cited by 6 · see citing works
Gains and losses on the road to understanding Alzheimer’s disease
Konietzko, U. (2015) · Swiss Medical Weekly · doi:10.4414/smw.2015.14233 · Cited by 6 · see citing works
Treatment with BRICHOS domain helps to clarify issues with Alzheimer mouse models
Johansson, J. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00041-1 · Cited by 5 · see citing works
Kabra, A. (2022) · International journal of high school research · doi:10.36838/v4i6.10 · Cited by 4 · see citing works
In Vivo Models for Evaluation of Drug Efficacy: Demand and Challenges
Asthana, S., Shukla, V., & Tripathi, A. (2023) · Springer eBooks · doi:10.1007/978-981-19-7952-1_5 · Cited by 4 · see citing works
Copper Chelation via beta-alanine extends lifespan in a C. elegans model of Alzheimer's Disease
Pulido, A., Hulbert, B., Giese, H., Kurian, S., Rozhon, R., Zambrano, M., Diaz, O. R., Abd, M., Caputo, M., Kissel, D. S., et al. (2023) · Brain Disorders · doi:10.1016/j.dscb.2023.100076 · Cited by 3 · see citing works
Presto, J., & Johansson, J. (2015) · Springer briefs in molecular science · doi:10.1007/978-3-319-16564-6_1 · Cited by 3 · see citing works
Moore, B. D., Levites, Y., Xu, G. M., Hampton, H., Adamo, M. F., Croft, C. L., Futch, H. S., Moran, C., Fromholt, S., Janus, C., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-1040944/v1 · Cited by 3 · see citing works
Self-citationMisfolded Protein Linked Strategies Toward Biomarker Development for Neurodegenerative Diseases
Kumar, S., Narayanan, K., Mishra, S., Padmanabhan, P., Radda, G. K., & Gulyás, B. Z. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1232-4 · Cited by 2 · see citing works
Neurodegenerative Diseases and Dementia
Janus, C., & Welzl, H. (2016) · Springer eBooks · doi:10.1007/978-1-4939-3777-6_6 · Cited by 2 · see citing works
Self-citationRahman, M., Akter, K., Rani, A., Park, M. N., & Kim, B. (2026) · Nutrients · doi:10.3390/nu18111796 · Cited by 1 · see citing works
Amyloid β-protein oligomers and Alzheimer's
Hayden, E. Y., & Teplow, D. B. (2013) · Cited by 1 · see citing works
Sex and the Aging Immune System
Gibson, D. C., & Bupp, M. G. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00059-2 · Cited by 1 · see citing works
Budyak, E. I., Kwon, J., Messenger, E. J., Maharjan, S., & Koothur, J. J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.06.552135 · Cited by 1 · see citing works
Islet amyloid polypeptide (IAPP) in Type 2 diabetes and Alzheimer disease
Oskarsson, M. E. (2015) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Frontiers in Clinical Drug Research - Alzheimer Disorders
Marei, H. E., Althani, A., Suhonen, J., El Zowalaty, M. E., Albanna, M. A., Cenciarelli, C., Wang, T., & Caceci, T. (2016) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/97816810823181160501
D'adamio, L. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00042-0
Exact relationship between Aβ40 and Aβ42: An overlooked discovery by Jungsu Kim and colleagues
Saido, T. C. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-28979-8.00018-8
Investigating the physiological function of the amyloid precursor protein in Drosophila melanogaster
Kesisoglou, E. (2020) · theses.fr (ABES) · doi:10.70675/691831c4z5491z4cb9zb88az10456e67b7ce
- Authors
- Kim, J., Chakrabarty, P., Hanna, A., March, A., Dickson, D. W., Borchelt, D. R., Golde, T., & Janus, C.
- Affiliations
- University of Florida (US)
- Mayo Clinic (US)
- Corresponding author
- Golde, Todd
- Janus, Christopher
- ORCID
- Venue
- Molecular Neurodegeneration
- Published
- 2013-05-12
- Volume
- 8
- Issue
- 1
- Pages
- 15-15
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC3658944
- OpenAlex
- W2140788457
- Semantic Scholar
- fd9e7ea5a3ab4a2d26beb1d734e0c5735789bbbe
- Cited by
- 83
- References
- 72
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 12 · 2018: 8 · 2017: 3 · 2016: 6 · 2015: 11 · 2014: 5 · 2013: 4
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Europe PMC (PubMed Central) (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by)
- Funders
- National Institute on Aging (R01AG018454)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, amyloid precursor protein, Aβ40, amyloid-beta 42, amyloid plaques, cognitive impairment, memory impairment, APP overexpression, amyloid fibril formation
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cognition, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunohistochemistry, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Recombinant Fusion Proteins, Blotting, Western, Amyloid beta-Peptides, Adaptor Proteins, Signal Transducing, Mice
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 2026-10-17.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-17.
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
