# APOE genotypes are associated with the level of naturally occurring antibodies to amyloid-β in patients with Alzheimer’s disease

**Authors:** Janardan P. Pandey, Aryan M. Namboodiri, Franca Rosa Guerini, Elisabetta Bolognesi, Milena Zanzottera, Roberta Mancuso, Simone Agostini

PMC · DOI: 10.3389/fnagi.2026.1673361 · Frontiers in Aging Neuroscience · 2026-02-10

## TL;DR

People with a specific APOE gene variant have higher levels of antibodies to a protein linked to Alzheimer's disease.

## Contribution

This study is the first to show a link between APOEε4 and naturally occurring anti-amyloid-beta antibodies in Alzheimer's patients.

## Key findings

- APOEε4 carriers had significantly higher anti-Aβ antibody levels than non-carriers.
- Regression analysis showed a marginal association between APOEε4 and anti-Aβ antibodies after adjusting for other factors.

## Abstract

Apolipoprotein E ε4 (APOEε4) allele is the strongest known genetic risk factor for Alzheimer’s disease (AD). Mechanisms underlying this association are incompletely understood. We aimed to determine whether APOE genotypes influenced the level of naturally occurring antibodies to amyloid-β (Aβ), a hallmark of AD, and whether anti-Aβ antibodies contributed to neurodegeneration, as measured by mini-mental state examination (MMSE) score. The study population consisted of 93 Italian AD patients. Results showed that APOEε4-carriers had significantly higher levels of anti-Aβ antibodies than non-carriers (p = 0.018). After adjusting for age, sex, Aβ levels in serum, and the MMSE scores, regression analyses showed marginal association between APOEε4 carrier status and the levels of anti-Aβ antibodies (p = 0.050). This is the first report of its kind and needs to be confirmed in a large multiethnic population.

## Linked entities

- **Genes:** APOE (apolipoprotein E) [NCBI Gene 348]
- **Proteins:** ab (abrupt)
- **Diseases:** Alzheimer’s disease (MONDO:0004975), AD (MONDO:0004975)

## Full-text entities

- **Genes:** ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}
- **Diseases:** vitamin deficiency syndromes (MESH:D014802), malnutrition (MESH:D044342), AD (MESH:D000544), neurodegeneration (MESH:D019636)
- **Chemicals:** PBS (-), hydrogen peroxide (MESH:D006861), tween 20 (MESH:D011136), memantine (MESH:D008559), 3,3',5,5'-Tetramethylbenzidine (MESH:C021758), HCl (MESH:D006851)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs429358, rs7412

## Full text

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## Figures

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## References

6 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929472/full.md

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Source: https://tomesphere.com/paper/PMC12929472