Evidence map›Paper›PMID 40884585›Full record

ArticleJournal of pharmacokinetics and pharmacodynamics2025

APOE4 genotypes and the trajectory of biomarkers, neuroimaging, and cognitive measures in Alzheimer's Disease: A mixed-effects disease progression model.

Carson Essenburg, Murali Ramanathan

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In one paragraph

Article in Journal of pharmacokinetics and pharmacodynamics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
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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

2 authors.

Carson EssenburgArtificial Intelligence & Clinical Pharmacology Laboratory, Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA.
Murali RamanathanArtificial Intelligence & Clinical Pharmacology Laboratory, Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA. Murali@Buffalo.Edu.

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

backgroundThe ε4 allele of the apolipoprotein E gene (APOE4) is a major risk factor for developing sporadic Alzheimer's disease (AD). APOE4 homozygosity has been recently proposed as the defining signature of a genetic form of AD. The goal was to assess the role, if any, of APOE4 in AD progression using a mixed-effects disease progression model-informed approach.

methodsData from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed for 2092 participants categorized as cognitively normal (CN), subjective memory concerns (SMC), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), or AD. Each included subject had a median of 5.00 (IQR: 3-8) follow-ups; there were n = 13,699 follow-ups. Demographics, APOE4 genotype, cerebrospinal fluid biomarkers, MRI measures, and neuropsychological tests from baseline to 6-years of follow-up visits were analyzed. Linear mixed-effects models were used to evaluate the impact of the APOE4 genotype on disease progression.

resultsAPOE4 heterozygous and homozygous frequencies were higher in AD vs. CN (p < 0.001). APOE4-positive groups were associated with lower levels of amyloid β1-42, higher levels of Tau and phosphorylated tau-181 proteins, lower hippocampus and entorhinal volumes, and worse AD Assessment Scale Cognitive-11 (ADAS-COG11), ADAS-COG13, and Mini-Mental State Examination neuropsychological test scores. The progression of the biomarkers over time was not associated with APOE4 positivity. The progression of all MRI measures and neuropsychological test scores was associated with APOE4 positivity.

conclusionsAPOE4 genotypes adversely influence the levels of biomarkers and the progression of neuroimaging and cognitive outcomes in AD.

Indexed as

Alzheimer DiseaseApolipoprotein E4CognitionAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersCognitive DysfunctionDisease ProgressionFemaleGenotypeHumansMagnetic Resonance ImagingMaleNeuroimagingNeuropsychological TestsAmyloid beta-PeptidesApolipoprotein E4Biomarkerstau ProteinsAlzheimer’s diseaseBiomarkersCognitiveDisease modelingDisease progressionImagingMixed effect modelModel-informed drug developmentPharmacometrics

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Registered trials

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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 Socratic graph.