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Record W3020556534 · doi:10.1101/741777

Inflammation in Alzheimer’s disease: do sex and APOE matter?

2019· preprint· en· W3020556534 on OpenAlexafffund
Paula Duarte‐Guterman, Arianne Albert, Amy M. Inkster, Cindy K. Barha, Liisa A.M. Galea

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldNeuroscience
TopicNuclear Receptors and Signaling
Canadian institutionsBC Children's HospitalWomen's Health Research InstituteUniversity of British Columbia
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Institutes of HealthHealth CanadaGenentechIXICOH. Lundbeck A/SServierEisaiGovernment of CanadaNorthern California Institute for Research and EducationFondation Brain CanadaPfizerBiogenBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaEli Lilly and CompanyU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationBristol-Myers SquibbAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsApolipoprotein EInflammationAlleleNeuropathologyInternal medicineGenotypeDiseaseEndocrinologyNeuroinflammationMedicinePsychologyBiologyGeneticsGene

Abstract

fetched live from OpenAlex

ABSTRACT Alzheimer’s disease (AD) disproportionately affects females with steeper cognitive decline and more neuropathology compared to males, which is exacerbated in females carrying the APOEε4 allele. The risk of developing AD is also higher in female APOEε4 carriers in earlier age groups (aged 65-75), and the progression from cognitively normal to mild cognitive impairment (MCI) and to AD may be influenced by sex. Inflammation is observed in AD and is related to aging, stress, and neuroplasticity, and although studies are scarce, sex differences are noted in inflammation. The objective of this study was to investigate underlying physiological inflammatory mechanisms that may help explain why there are sex differences in AD and APOEε4 carriers. We investigated, using the ADNI database, the effect of sex and APOE genotype (non-carriers or carriers of 1 and 2 APOEε4 alleles) and sex and diagnosis (cognitively normal (CN), MCI, AD) on CSF (N= 279) and plasma (N= 527) markers of stress and inflammation. We found CSF IL-16 and IL-8 levels were significantly lower in female non-carriers of APOEε4 alleles compared to males, whereas levels were similar between the sexes among carriers of APOEε4 alleles. Furthermore, females had on average higher levels of plasma CRP and ICAM1 but lower levels of CSF ICAM1, IL-8, IL-16, and IgA than males. Carrying APOEε4 alleles and diagnosis (MCI and AD) decreased plasma CRP in both sexes. Sex differences in inflammatory biomarkers support that the underlying physiological changes during aging differ by sex and tissue origin.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.179
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.021
GPT teacher head0.231
Teacher spread0.211 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations6
Published2019
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicNuclear Receptors and SignalingFrench-language works237,207