Evidence map›Paper›PMID 27814296›Full record

ArticleJournal of Alzheimer's disease : JAD2017

Early Evidence of Low Bone Density and Decreased Serotonergic Synthesis in the Dorsal Raphe of a Tauopathy Model of Alzheimer's Disease.

Christine M Dengler-Crish, Matthew A Smith, Gina N Wilson

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
4.1field-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, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

  1. Pooled it
  2. Dorsal raphe tau pathology disrupts sleep-wake orchestration and sleep architecture in a sex-specific manner.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
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.

Christine M Dengler-CrishDepartment of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA.
Matthew A SmithDepartment of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA.
Gina N WilsonDepartment of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA.
Northeast Ohio Medical University · USKent State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Reduced bone mineral density (BMD) and its clinical sequelae, osteoporosis, occur at a much greater rate in patients with Alzheimer's disease (AD), often emerging early in the disease before significant cognitive decline is seen. Reduced BMD translates to increased bone fracture risk, decreased quality of life, and increased mortality for AD patients. However, the mechanism responsible for this observation is unclear. We hypothesize that bone loss is an additional component of an AD prodrome-changes that emerge prior to dementia and are mediated by dysfunction of the central serotonergic pathways. We characterized the skeletal phenotype of htau mice that express human forms of the microtubule-associated protein tau that become pathologically hyperphosphorylated in AD. Using radiographic densitometry, we measured BMD in female and male htau mice from 2-6 months of age-time-points prior to the presence of significant tauopathy in the hippocampal/entorhinal regions characteristic of this model. We found a significantly reduced BMD phenotype in htau mice that was most pronounced in males. Using western blotting and immunofluorescence, we showed overall reduced tryptophan hydroxylase (TPH) protein in htau brainstem and a 70% reduction in TPH-positive cells in the dorsal raphe nucleus (DRN)-a pivotal structure in the regulation of the adult skeleton. Elevations of hyperphosphorylated tau (ptau) proteins were also measured in brainstem, and co-labeled immunofluorescence studies showed presence of ptau in TPH-positive cells of the DRN as early as 4 months of age in htau mice. Together, these findings demonstrate that reduced BMD occurs earlier than overt degeneration in a tau-based AD model and that pathological changes in tau phosphorylation occur in the serotonin-producing neurons of the brainstem raphe in these mice. This illuminates a need to define a mechanistic relationship between bone loss and serotonergic deficits in early AD.

Indexed as

Alzheimer DiseaseAge FactorsAnimalsBody CompositionBody WeightBone DensityBone DiseasesDisease Models, AnimalDorsal Raphe NucleusFemaleMaleMiceMice, Inbred C57BLMice, TransgenicNeuronsPhosphorylationSerotonintau ProteinsTryptophan HydroxylaseAlzheimer’s diseasebone densitymicrotubule-associated proteinserotonintauopathiestau proteins

Identifiers

PMID27814296
PMCPMC5181667
OpenAlexW2547969205

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.