Evidence map›Paper›PMID 19252918›Full record

ArticleActa neuropathologica2009

Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin.

Kiren Ubhi, Edward Rockenstein, Edith Doppler, Michael Mante, Anthony Adame, Christina Patrick, Margarita Trejo, Leslie Crews, Amy Paulino, Herbert Moessler and 1 more

Expression of concernOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 10% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Review
  6. Article
  7. Genetic Insights into Alzheimer's Disease.Annual review of pathology · 2021
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Gene Therapy Models of Alzheimer's Disease and Other Dementias.Methods in molecular biology (Clifton, N.J.) · 2016
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Kiren UbhiDepartment of Neurosciences, School of Medicine, University of California, La Jolla, San Diego, CA 92093-0624, USA.
Edward Rockenstein
Edith Doppler
Michael Mante
Anthony Adame
Christina Patrick
Margarita Trejo
Leslie Crews
Amy Paulino
Herbert Moessler
Eliezer Masliah
University of California, San Diego · USEVER Neuro Pharma (Austria) · AT

Funding

VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
NIA NIH HHS AG05131NIA NIH HHS P50 AG005131
6 · The paper itself

Abstract

Alzheimer's disease (AD) continues to be the most common cause of cognitive and motor alterations in the aging population. Accumulation of amyloid beta (Abeta)-protein oligomers and the microtubule associated protein-TAU might be responsible for the neurological damage. We have previously shown that Cerebrolysin (CBL) reduces the synaptic and behavioral deficits in amyloid precursor protein (APP) transgenic (tg) mice by decreasing APP phosphorylation via modulation of glycogen synthase kinase-3beta (GSK3beta) and cyclin-dependent kinase-5 (CDK5) activity. These kinases also regulate TAU phosphorylation and are involved in promoting neurofibrillary pathology. In order to investigate the neuroprotective effects of CBL on TAU pathology, a new model for neurofibrillary alterations was developed using somatic gene transfer with adeno-associated virus (AAV2)-mutant (mut) TAU (P301L). The Thy1-APP tg mice (3 m/o) received bilateral injections of AAV2-mutTAU or AAV2-GFP, into the hippocampus. After 3 months, compared to non-tg controls, in APP tg mice intra-hippocampal injections with AAV2-mutTAU resulted in localized increased accumulation of phosphorylated TAU and neurodegeneration. Compared with vehicle controls, treatment with CBL in APP tg injected with AAV2-mutTAU resulted in a significant decrease in the levels of TAU phosphorylation at critical sites dependent on GSK3beta and CDK5 activity. This was accompanied by amelioration of the neurodegenerative alterations in the hippocampus. This study supports the concept that the neuroprotective effects of CBL may involve the reduction of TAU phosphorylation by regulating kinase activity.

Indexed as

Amino AcidsAmyloid beta-Protein PrecursorAnimalsCell Line, TumorDependovirusGenetic VectorsGene Transfer TechniquesHippocampusHumansMiceMice, TransgenicNerve DegenerationNeurodegenerative DiseasesNeurofibrillary TanglesNeuronsNeuroprotective AgentsAmino AcidsAmyloid beta-Protein PrecursorAPP protein, humancerebrolysinMAPT protein, humanNeuroprotective AgentsProtease NexinsReceptors, Cell Surfacetau Proteins

Identifiers

PMID19252918
PMCPMC3049872
OpenAlexW2135724524

What OpenQuestion holds

Textmetadata
LicenceTDM
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.