Oligomers of the amyloid-β protein disrupt working memory: Confirmation with two behavioral procedures

Poling, Alan; Morgan-Paisley, Kineta Lynn; Panos, J; Kim, Eun-Mee; O’Hare, Eugene; Cleary, J.; Lesné, Sylvain; Ashe, Karen H.; Porritt, Matthew; Baker, Lisa E.

doi:10.1016/j.bbr.2008.06.001

Cited by 69 publications

(60 citation statements)

References 34 publications

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“…Thus far, there are only a few reports of the in vivo involvement of Aβ oligomers in memory impairment in rats (9)(10)(11)(12). Several types of Aβ aggregate isolated from biological sources have been used in these studies.…”

mentioning

confidence: 99%

Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein

Balducci¹,

Beeg

Stravalaci

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

436

438

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Inability to form new memories is an early clinical sign of Alzheimer's disease (AD). There is ample evidence that the amyloid-β (Aβ) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of Aβ are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Aβ−mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Aβ 1-42 oligomers impaired consolidation of the long-term recognition memory, whereas mature Aβ 1-42 fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Aβ antibody. It has been suggested that the cellular prion protein (PrP C ) mediates the impairment of synaptic plasticity induced by Aβ. We confirmed that Aβ 1-42 oligomers interact with PrP C , with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Aβ 1-42 oligomers are responsible for cognitive impairment in AD and that PrP C is not required.Alzheimer | neurotoxicity | object recognition test | surface plasmon resonance | protein aggregation

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mentioning

confidence: 99%

Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein

Balducci¹,

Beeg

Stravalaci

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

436

438

View full text Add to dashboard Cite

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“…One of the characteristics of this disease is the presence of extracellular senile plaques principally composed of aggregated species of amyloid-␤ peptide (A␤), a 39 to 42 amino acid peptide produced by the cleavage action of ␤ and ␥ secretases on the amyloid-␤ protein precursor (A␤PP). The oligomeric and aggregated states of A␤ have been implicated in the synaptotoxicity and neurodegeneration found in the brain of AD patients [1,2]. It has been demonstrated that aggregated A␤ inhibits synaptic plasticity and decreases long term potentiation (LTP) and dendritic spine density in rat hippocampal slices [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Soluble Aβ1-40 Peptide Increases Excitatory Neurotransmission and Induces Epileptiform Activity in Hippocampal Neurons

Cuevas

Haensgen

Sepúlveda

et al. 2011

JAD

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Abstract. It is believed that amyloid-␤ peptide (A␤), in its aggregated-oligomeric state, constitutes one of the neurotoxic factors involved in the pathogenesis of Alzheimer's disease. With the objective of studying a potential role of the peptide on synaptic transmission, we studied the effect of soluble A␤ 1-40 on synaptic transmission in rat hippocampal neurons. Neurons incubated with 500 nM of A␤ 1-40 peptide for 3 days presented higher levels of intracellular calcium transients, as evaluated by fluorimetric techniques. These effects of A␤ were time and concentration dependent and were accompanied by increases in glutamatergic (0.8 ± 0.2 Hz to 2.9 ± 0.6 Hz), but not GABAergic, transmission. The analysis of pharmacologically isolated currents in treated neurons showed increases in both AMPA-and NMDA-mediated currents as compared to control. The effects of the peptide on the frequency of synaptic currents correlated well with increases in the number of SV2 puncta and of FM1-43 destaining, suggesting a presynaptic locus for the peptide. The data also shows that application of either A␤ or bicuculline alone for 24 h was without effects on neurotransmission. However, their co-application induced an increase in synaptic transmission which was accompanied by synchronous discharges reminiscent to those produced by pro-convulsive drugs, such as bicuculline. In conclusion, these results suggest that the soluble form of A␤ 1-40 participates in the regulation of synaptic transmission increasing excitability and producing a pre-epileptogenic state in hippocampal neurons.

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“…Among these is the soluble form of Aβ*56 which has been shown to be negatively associated with cognitive decline in an APP transgenic mouse model [117] and when injected into the rat brain [118]. Consequently, the original amyloid hypothesis of Hardy and Selkoe [113] has been modified to the 'Aβ oligomer hypothesis' as originally termed by Ono et al [115].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Apolipoprotein E Related Co-Morbidities and Alzheimer’s Disease

Singhrao

Harding

Chukkapalli

et al. 2016

JAD

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The primary goal of advancement in clinical services is to provide a health care system that enhances an individual's quality of life. Incidence of diabetes mellitus, cardiovascular disease and associated dementia coupled with the advancing age of the population, have led to an increase in the worldwide challenge to the healthcare system. In order to overcome these challenges prior knowledge of common, reliable risk factors and their effectors is essential. The oral health constitutes one such relatively unexplored but indispensable risk factor for aforementioned co-morbidities, in the form of poor oral hygiene and tooth loss during aging.Behavioural traits such as low education, smoking, poor diet, neglect of oral health, lack of exercise, and hypertension are few of the risk factors that are shared commonly amongst these conditions. In addition, common genetic susceptibility traits such as the apolipoprotein ɛ gene, together with an individual's life style can also influence the development of co-morbidities such as periodontitis, atherosclerosis/stroke, diabetes, and Alzheimer's disease. This review specifically addresses the susceptibility of apolipoprotein ε gene allele 4 as the plausible commonality for the etiology of co-morbidities that eventually result from periodontal diseases and ultimately progress to dementia.

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Oligomers of the amyloid-β protein disrupt working memory: Confirmation with two behavioral procedures

Cited by 69 publications

References 34 publications

Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein

Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein

Soluble Aβ1-40 Peptide Increases Excitatory Neurotransmission and Induces Epileptiform Activity in Hippocampal Neurons

Apolipoprotein E Related Co-Morbidities and Alzheimer’s Disease

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