Evidence map›Paper›PMID 27177549›Full record

ArticleMolecular neurobiology2017

Progressive Neuronal Pathology and Synaptic Loss Induced by Prediabetes and Type 2 Diabetes in a Mouse Model of Alzheimer's Disease.

Juan Jose Ramos-Rodriguez, Tara Spires-Jones, Amy M Pooler, Alfonso Maria Lechuga-Sancho, Brian J Bacskai, Monica Garcia-Alloza

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

40 citing papers in PubMed, 69 citations in OpenAlex.

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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

6 authors at 3 institutions in 3 countries.

Juan Jose Ramos-RodriguezDivision of Physiology, School of Medicine, Universidad de Cadiz, Cadiz, Spain.
Tara Spires-JonesDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Amy M PoolerDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Alfonso Maria Lechuga-SanchoDepartment of Pediatrics, School of Medicine, Universidad de Cadiz, Cadiz, Spain.
Brian J BacskaiDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Monica Garcia-AllozaDivision of Physiology, School of Medicine, Universidad de Cadiz, Cadiz, Spain. monica.garcia@uca.es.
Universidad de Cádiz · ESHarvard University · USMassachusetts General Hospital · US

Funding

Alzheimer's Society 195
6 · The paper itself

Abstract

Age remains the main risk factor for developing Alzheimer's disease (AD) although certain metabolic alterations, including prediabetes and type 2 diabetes (T2D), may also increase this risk. In order to understand this relationship, we have studied an AD-prediabetes mouse model (APP/PS1) with severe hyperinsulinemia induced by long-term high fat diet (HFD), and an AD-T2D model, generated by crossing APP/PS1 and db/db mice (APP/PS1xdb/db). In both, prediabetic and diabetic AD mice, we have analyzed underlying neuronal pathology and synaptic loss. At 26 weeks of age, when both pathologies were clearly established, we observed severe brain atrophy in APP/PS1xdb/db animals as well as cortical thinning, accompanied by increased caspase activity. Reduced senile plaque burden and elevated soluble Aβ40 and 42 levels were observed in AD-T2D mice. Further assessment revealed a significant increase of neurite curvature in prediabetic-AD mice, and this effect was worsened in AD-T2D animals. Synaptic density loss, analyzed by array tomography, revealed a synergistic effect between T2D and AD, whereas an intermediate state was observed, once more, in prediabetic-AD mice. Altogether, our data suggest that early prediabetic hyperinsulinemia may exacerbate AD pathology, and that fully established T2D clearly worsens these effects. Therefore, it is feasible that early detection of prediabetic state and strict metabolic control could slow or delay progression of AD-associated neuropathological features.

Indexed as

Alzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsAtrophyCaspasesDiabetes Mellitus, Type 2Disease Models, AnimalEnzyme ActivationMice, TransgenicNeuritesNeuronsPlaque, AmyloidPrediabetic StatePresenilin-1SynapsesAmyloid beta-Protein PrecursorCaspasesPresenilin-1Alzheimer’s diseaseArray tomographyAxonal curvatureHyperinsulinemiaSynaptic densityType 2 diabetes

Identifiers

PMID27177549
OpenAlexW2382076021

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.