Evidence map›Paper›PMID 39143322›Full record

ArticleMolecular psychiatry2025

Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer's disease.

Samantha R Pierson, Kimberly L Fiock, Ruixiang Wang, Nagalakshmi Balasubramanian, Jessica Reinhardt, Kanza M Khan, Thomas D James, Mikayla L Hunter, Benjamin J Cooper, Hannah R Williamsen and 6 more

Abstract read
In one paragraph

Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

20 citing papers in PubMed, 1 synthesis or guideline pooled it.

  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. Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026
    Review
  7. Alzheimer's Pathology Enhances Excitatory Synaptic Input and Integration in VTA Dopamine Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  8. Article
  9. Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  10. The neuromodulatory fragility hypothesis of Alzheimer's disease pathogenesis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  11. Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  12. Eagle eyes on the human brain and beyond: PET at ultra-high spatial resolution.European journal of nuclear medicine and molecular imaging · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. A New Insight into the Role of CART Peptide in Serotonergic Function and Anxiety.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  17. Review
  18. Article
  19. Article
  20. Review
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

16 authors.

Samantha R PiersonDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, 52242, USA.ORCID 0000-0002-8376-4465
Kimberly L FiockDepartment of Pathology, University of Iowa, Iowa City, IA, 52242, USA.ORCID 0000-0002-5376-1589
Ruixiang WangDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, 52242, USA.
Nagalakshmi BalasubramanianDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, 52242, USA.
Jessica ReinhardtDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, 52242, USA.
Kanza M KhanPsychological Sciences Department, Daemen University, Amherst, NY, 14226, USA.ORCID 0000-0003-4018-7669
Thomas D JamesDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, 52242, USA.ORCID 0000-0003-0949-4783
Mikayla L HunterDepartment of Pathology, University of Iowa, Iowa City, IA, 52242, USA.
Benjamin J CooperDepartment of Pathology, University of Iowa, Iowa City, IA, 52242, USA.ORCID 0000-0002-4758-3261
Hannah R WilliamsenDepartment of Pathology, University of Iowa, Iowa City, IA, 52242, USA.
Ryan BettersDepartment of Pathology, University of Iowa, Iowa City, IA, 52242, USA.
Kaancan DenizDepartment of Neurology, University of Iowa, Iowa City, IA, 52242, USA.ORCID 0000-0002-5496-0598
Gloria LeeDepartment of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.ORCID 0000-0002-8633-1534
Georgina AldridgeDepartment of Neurology, University of Iowa, Iowa City, IA, 52242, USA.
Marco M HeftiDepartment of Pathology, University of Iowa, Iowa City, IA, 52242, USA.
Catherine A MarcinkiewczDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, 52242, USA. catherine-marcinkiewcz@uiowa.edu.ORCID 0000-0001-7161-7815

Funding

Multidisciplinary Lung Research Career Development ProgramT32HL007638 · NHLBI · UNIVERSITY OF IOWA · PI WELSH, MICHAEL J., ZABNER, JOSEPH · 1986 to 2020
$16.9M
Diabetes Research Training Program Diversity SupplementT32DK112751 · NIDDK · UNIVERSITY OF IOWA · PI Andrew W Norris · 2017 to 2026
$4.8M
Predoctoral Training in the Pharmacological SciencesT32GM067795 · NIGMS · UNIVERSITY OF IOWA · PI STRACK, STEFAN · 2004 to 2021
$3.4M
Sleep and affective disturbances in the etiology of Alzheimer's diseaseR01AG070841 · NIA · UNIVERSITY OF IOWA · PI MARCINKIEWCZ, CATHERINE ANNE · 2021 to 2025
$2.8M
Predoctoral Training in the Pharmacological SciencesT32GM144636 · NIGMS · UNIVERSITY OF IOWA · PI David L. Roman, STEFAN STRACK · 2022 to 2026
$1.9M
Alcohol and the Serotonin System in the Progression of Alzheimer's DiseaseR01AA028931 · NIAAA · UNIVERSITY OF IOWA · PI MARCINKIEWCZ, CATHERINE ANNE · 2020 to 2024
$1.9M
A non-canonical role for tau in early human brain developmentR01NS136448 · NINDS · UNIVERSITY OF IOWA · PI Marco Matthias Hefti · 2024 to 2026
$1.6M
Novel tau-based diagnostics for neonatal hypoxic-ischemic injuryK23NS109284 · NINDS · UNIVERSITY OF IOWA · PI HEFTI, MARCO MATTHIAS · 2019 to 2023
$950k
NHLBI NIH HHS T32 HL007638NIAAA NIH HHS R01 AA028931NIA NIH HHS R01 AG070841NIDDK NIH HHS T32 DK112751NIGMS NIH HHS T32 GM067795NIGMS NIH HHS T32 GM144636NINDS NIH HHS K23 NS109284NINDS NIH HHS R01 NS136448U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01 AG070841),
6 · The paper itself

Abstract

Protein aggregation in brainstem nuclei is thought to occur in the early stages of Alzheimer's disease (AD), but its specific role in driving prodromal symptoms and disease progression is largely unknown. The dorsal raphe nucleus (DRN) contains a large population of serotonin (5-hydroxytryptamine; 5-HT) neurons that regulate mood, reward-related behavior, and sleep, which are all disrupted in AD. We report here that tau pathology is present in the DRN of individuals 25-80 years old without a known history of dementia, and its prevalence was comparable to the locus coeruleus (LC). By comparison, fewer cases were positive for other pathological proteins including α-synuclein, β-amyloid, and TDP-43. To evaluate how early tau pathology impacts behavior, we overexpressed human P301L-tau in the DRN of mice and observed depressive-like behaviors and hyperactivity without deficits in spatial memory. Tau pathology was predominantly found in neurons relative to glia and colocalized with a significant proportion of Tph2-expressing neurons in the DRN. 5-HT neurons were also hyperexcitable in P301L-tau

Indexed as

Alzheimer DiseaseDorsal Raphe Nucleustau ProteinsAdultAgedAged, 80 and overalpha-SynucleinAmyloid beta-PeptidesAnimalsFemaleHumansLocus CoeruleusMaleMiceMice, TransgenicMiddle Agedalpha-SynucleinAmyloid beta-PeptidesSerotonintau Proteins

Identifiers

PMID39143322
PMCPMC12010729

What OpenQuestion holds

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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.