Evidence map›Paper›PMID 40095666›Full record

ArticleJournal of Alzheimer's disease : JAD2025

The neuropathologic basis for translational biomarker development in the macaque model of late-onset Alzheimer's disease.

Caroline J Zeiss, Anita Huttner, Angus C Nairn, Amy Arnsten, Dibyadeep Datta, Stephen M Strittmatter, Brent Vander Wyk, Alvaro Duque

Abstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. 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

8 authors.

Caroline J ZeissDepartment of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0003-1181-3544
Anita HuttnerDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0003-2143-4329
Angus C NairnDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-7075-0195
Amy ArnstenDepartment of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-3420-1308
Dibyadeep DattaDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-5415-3067
Stephen M StrittmatterDepartment of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0001-8188-3092
Brent Vander WykDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0003-3990-3955
Alvaro DuqueDepartment of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-5086-5438

Funding

Yale Study Support Suite (YES3): Dashboard and Web Portal Software Supporting Research Workflow through integrated, customizable REDCap External ModulesP30AG021342 · NIA · YALE UNIVERSITY · PI Lauren Ferrante · 2002 to 2026
$37.9M
Yale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER · 2020 to 2026
$30.2M
Yale Macaque Brain ResourceR01MH113257 · NIMH · YALE UNIVERSITY · PI Alvaro Duque · 2017 to 2026
$4.3M
NIA NIH HHS P30 AG021342NIA NIH HHS P30 AG066508NIMH NIH HHS R01 MH113257
6 · The paper itself

Abstract

BackgroundAccurate placement of the macaque within the Alzheimer's disease (AD) research framework is essential to discover early-stage predictive biomarkers.ObjectiveTo assess utility of the aging macaque in advancing translational biomarker development for preclinical AD, we evaluated relative signal strength of comparable neuropathologic phenomena in macaques and patients.MethodsWe compared pathology in patient and macaque formalin-fixed paraffin embedded (FFPE) tissues using identical criteria. We quantified expression of amyloid-β (Aβ), pTau, and inflammatory and senescence markers across species. Distribution of AD-relevant markers were compared in FFPE and perfused frozen macaque brain to assess expression of labile proteins that could inform in-life fluid biomarkers.ResultsAβ pathology in macaques closely approximated patient pathology. Complex plaque composition in macaques implied significant disruption of synaptic connectivity. In FFPE tissue, pretangle pTau immunoreactivity placed the macaque in Braak Stage 1b. In perfused frozen tissue, soluble pTau distribution approximated Braak Stage III-IV. In macaque, Aβ, pTau, and acetylcholinesterase labeling co-localized to AD-vulnerable circuits. Significant association of glial fibrillary acidic protein with Aβ occurred in humans only. The senescence marker p16 correlated positively with pTau expression and negatively with Aβ in patients only. Macaques lacked neuropathologic co-morbidities.ConclusionsAD-relevant neuropathologic signals in the macaque support biomarker discovery in the areas of Aβ plaque evolution and associated synaptic disruption as well as early-stage tau phosphorylation. Relative protection from accumulation of senescence markers, fibrillar tau and neuropathologic co-morbidities in macaque implicate species difference in rates of biological brain aging. We provide over 4000 digital slides for further study.

Indexed as

Alzheimer DiseaseBrainAgedAged, 80 and overAmyloid beta-PeptidesAnimalsBiomarkersDisease Models, AnimalFemaleHumansMacaca mulattaMalePlaque, Amyloidtau ProteinsTranslational Research, BiomedicalAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer's diseaseamyloid-βbiomarkerinflammatorymacaqueneuropathologypreclinicalsenescencetautranslational

Identifiers

PMID40095666
PMCPMC12380261

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.