Evidence map›Paper›PMID 18165846›Full record

ReviewThe journal of nutrition, health & aging2008

Why Alzheimer's is a disease of memory: the attack on synapses by A beta oligomers (ADDLs).

K L Viola, P T Velasco, W L Klein

Abstract readReview
PubMed Publisher
In one paragraph

Review in The journal of nutrition, health & aging, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
6.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 96 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Protein Oxidation in Aging and Alzheimer's Disease Brain.Antioxidants (Basel, Switzerland) · 2024
    Review
  5. Review
  6. Article
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  12. Article
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  14. Amyloid β synaptotoxicity is Wnt-PCP dependent and blocked by fasudil.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2018
    Article
  15. Effect of Qingxin Kaiqiao Fang on Hippocampus mRNA Expression of the Inflammation-Related Genes IL-1Evidence-based complementary and alternative medicine : eCAM · 2018
    Article
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

K L ViolaDepartment of Neurobiology and Physiology, Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Evanston, IL 60208, USA.
P T Velasco
W L Klein
Alzheimer’s Disease Neuroimaging Initiative · USNorthwestern University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Individuals with early-stage Alzheimer's disease (AD) suffer from profound failure to form new memories. A novel molecular mechanism with implications for therapeutics and diagnostics is now emerging in which the specificity of AD for memory derives from disruption of plasticity at synapses targeted by neurologically active A beta oligomers (1). We have named these oligomers "ADDLs" (for pathogenic A beta-Derived Diffusible Ligands). ADDLs constitute metastable alternatives to the disease-defining A beta fibrils deposited in amyloid plaques. In AD brain, ADDLs accumulate primarily as A beta 12mers (2) (approximately 54 kDa) and can be found in dot-like clusters distinct from senile plaques (3). Oligomers of equal mass have been reported to occur in tgmouse AD models where they emerge concomitantly with memory failure (4), consistent with ADDL inhibition of LTP (1). In cell biology studies, ADDLs act as pathogenic gain-of-function ligands that target particular synapses, binding to synaptic spines at or near NMDA receptors (5,6). Binding produces ectopic expression of the memory-linked immediate early gene Arc. Subsequent ADDL-induced abnormalities in spine morphology and synaptic receptor composition (7) are predicted consequences of Arc overexpression, a pathology associated with memory dysfunction in tg-Arc mice. Significantly, the attack on synapses provides a plausible mechanism unifying memory dysfunction with major features of AD neuropathology; recent findings show that ADDL binding instigates synapse loss, oxidative damage, and AD-type tau hyperphosphorylation. Acting as novel neurotoxins that putatively account for memory loss and neuropathology, ADDLs present significant targets for disease-modifying therapeutics in AD.

Indexed as

MemoryAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesBrain ChemistryHumansLigandsNeural PathwaysNeuronsSynapsesAmyloid beta-PeptidesLigands

Identifiers

PMID18165846
OpenAlexW1973552295

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.