Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus

Wang, Hai Wei; Pasternak, Joseph F.; Kuo, Helen; Ristic, Helen; Lambert, Mary P.; Chromy, Brett A.; Viola, Kirsten L.; Klein, William L.; Stine, W. Blaine; Krafft, Grant A.; Trommer, Barbara L.

doi:10.1016/s0006-8993(01)03058-x

Cited by 496 publications

(411 citation statements)

References 42 publications

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“…This time frame approximates the rapid LTP inhibition and cognitive disruption induced by 7PA2-CM. Inhibition of LTP occurred within 1 hour of administering 7PA2-CM in vivo or in slices (Townsend, et al, 2006;Walsh, et al, 2002a;Wang, et al, 2002); and impairment of cognition occurred within 1 day of administering 7PA2-CM in vivo (Cleary, et al, 2005). Thus, the Aβ-induced alterations in synaptic morphology described here could potentially represent a cellular substrate for impaired synaptic plasticity.…”

Section: Discussionmentioning

confidence: 77%

“…These cells were previously shown to secrete all natural derivatives of APP metabolism, including monomers, SDS-stable low-n oligomers, and soluble APP, but no detectable Aβ fibrils (Podlisny, et al, 1995;Walsh, et al, 2002b). Exposure of brain tissue to low concentrations of this medium inhibited the induction of LTP in vivo (Walsh, et al, 2002a) and in hippocampal slices (Townsend, et al, 2006;Wang, et al, 2002), and induced cognitive deficits in vivo (Cleary, et al, 2005). Walsh et al (2002a) and Cleary et al (2005) presented evidence that low-n oligomers of Aβ, not monomers or soluble fragments of APP, are responsible for the observed deficits on LTP and behavior.…”

Section: Discussionmentioning

confidence: 97%

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Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-β protein

Calabrese

Shaked

Tabarean

et al. 2007

Molecular and Cellular Neuroscience

120

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In Alzheimer's disease increasing evidence attributes synaptic and cognitive deficits to soluble oligomers of amyloid β protein (Aβ), even prior to the accumulation of amyloid plaques, neurofibrillary tangles, and neuronal cell death. Here we show that within 1-2 hours picomolar concentrations of cell-derived, soluble Aβ induce specific alterations in pre-and postsynaptic morphology and connectivity in cultured hippocampal neurons. Clusters of presynaptic vesicle markers decreased in size and number at glutamatergic but not GABAergic terminals. Dendritic spines also decreased in number and became dysmorphic, as spine heads collapsed and/or extended long protrusions. Simultaneous time-lapse imaging of axon-dendrite pairs revealed that shrinking spines sometimes became disconnected from their presynaptic varicosity. Concomitantly, miniature synaptic potentials decreased in amplitude and frequency. Spine changes were prevented by blockers of nAChRs and NMDARs. Washout of Aβ within the first day reversed these spine changes. Further, spine changes reversed spontaneously by two days, because neurons acutely developed resistance to continuous Aβ exposure. Thus, rapid Aβ-induced synapse destabilization may underlie transient behavioral impairments in animal models, and early cognitive deficits in Alzheimer's patients.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 97%

Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-β protein

Calabrese

Shaked

Tabarean

et al. 2007

Molecular and Cellular Neuroscience

120

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“…Complementary glutamatergic changes are likely involved in age-related memory impairments, potentially via reduced Reelin-mediated modulation of NMDA receptor activity and LTP Chen et al, 2005;Weeber et al, 2002). It is conceivable that age-related reductions of Reelin indirectly affect cognitive performances by favoring the production of soluble Aβ species, shown to impair LTP (Rowan et al, 2005;Walsh et al, 2002;Wang et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Age-related accumulation of Reelin in amyloid-like deposits

Knuesel

Nyffeler

Mormède

et al. 2009

Neurobiology of Aging

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Age-related accumulation of Reelin in amyloid-like deposits Abstract Accumulating evidence suggest that alterations in Reelin-mediated signaling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in rodents and primates is accompanied by accumulation of Reelin-enriched proteinous aggregates in the hippocampal formation that are related to the loss of Reelin-expressing neurons. Both phenomena are associated with age-related memory impairments in wild-type mice. We provide evidence that normal aging involves loss of Reelin neurons, reduced production and elimination of the extracellular deposits, whereas a prenatal immune challenge or the expression of AD-causing gene products, result in earlier, higher, and more persistent levels of Reelin-positive deposits. These aggregates co-localize with non-fibrillary amyloid-plaques, potentially representing oligomeric Abeta species. Our findings suggest that elevated Reelin plaque load creates a precursor condition for senile plaque deposition and may represent a critical risk factor for sporadic AD. ABSTRACTAccumulating evidence suggest that alterations in Reelin-mediated signalling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in rodents and primates is accompanied by accumulation of Reelin-enriched proteinous aggregates in the hippocampal formation that are related to the loss of Reelin-expressing neurons. Both phenomena are associated with age-related memory impairments in wild-type mice. We provide evidence that normal aging involves loss of Reelin neurons, reduced production and elimination of the extracellular deposits, whereas a prenatal immune challenge or the expression of AD-causing gene products, result in earlier, higher, and more persistent levels of Reelin-positive deposits.These aggregates co-localize with non-fibrillary amyloid-plaques, potentially representing oligomeric Aβ species. Our findings suggest that elevated Reelin plaque load creates a precursor condition for senile plaque deposition and may represent a critical risk factor for sporadic AD.3

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“…45 These secreted oligomers of Ab can interact with neurons, altering their electrical activity and normal physiology. 45 In view of these considerations, we generated Ab oligomers from the arctic mutant Ab 1À42 E22G 47 ( Figure 6h). Then, the toxicity in hippocampal neurons was measured.…”

Section: Hyp Protected From Ab-neurotoxicity In Vitromentioning

confidence: 99%

Hyperforin prevents β-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-β-deposits

Dinamarca¹,

Cerpa²,

Garrido

et al. 2006

Mol Psychiatry

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The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid b-peptide (Ab). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on Ab-induced spatial memory impairments and on Ab neurotoxicity. We report here that hyperforin: (1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; (2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; (3) prevents Ab-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and Ab oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease Ab aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease.

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Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus

Cited by 496 publications

References 42 publications

Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-β protein

Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-β protein

Age-related accumulation of Reelin in amyloid-like deposits

Hyperforin prevents β-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-β-deposits

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