Evidence map›Paper›PMID 23183882›Full record

ReviewNature reviews. Neurology2013

Deciphering the mechanism underlying late-onset Alzheimer disease.

Dimitrije Krstic, Irene Knuesel

Open access · hybridAbstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 230 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
230citing papers in PubMed, 7 pooled it
20.7field-weighted citation impact, top 1% 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

230 citing papers in PubMed, 7 syntheses or guidelines pooled it, 459 citations in OpenAlex.

  1. Association between Periodontal Disease and Cognitive Impairment in Adults.International journal of environmental research and public health · 2023
    Pooled it
  2. The cellular model for Alzheimer's disease research: PC12 cells.Frontiers in molecular neuroscience · 2022
    Pooled it
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  5. Influence of four polymorphisms in ABCA1 and PTGS2 genes on risk of Alzheimer's disease: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2016
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170 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

Dimitrije KrsticInstitute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Irene Knuesel
University of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-β (Aβ) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between Aβ and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence of Aβ accumulation in late-onset AD.

Indexed as

AgedAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainCell DeathDisease Models, AnimalDisease ProgressionHumansInflammation MediatorsMiceNeuritesNeurofibrillary TanglesProteostasis Deficienciestau ProteinsAmyloid beta-PeptidesInflammation MediatorsMAPT protein, humantau Proteins

Identifiers

PMID23183882
OpenAlexW1964117773

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.