| Title: | Can we identify people with Alzheimer's disease from examination of the eye? A bidirectional Mendelian randomization (MR) study |
| Journal: | The Journal of Prevention of Alzheimer's Disease |
| Published: | 10 Jul 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42430965/ |
| DOI: | https://doi.org/10.1016/j.tjpad.2026.100635 |
Publication 20312
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Abstract
BACKGROUND: Neurodegeneration in Alzheimer's disease (AD) is thought to be driven by amyloid-beta and tau deposition in the cerebral vasculature and brain. As the eye is an extension of the central nervous system, this study aimed to determine which neurovascular and neuroretinal changes in the eye are caused by AD rather than associations of the disease.</p>
METHODS: Bidirectional two-sample univariable and multivariable Mendelian randomization (MR) methods were applied. Instrumental variables were derived from genome-wide association studies (GWAS) of AD and the following ocular features: thickness measurements of central macula (MT), retinal nerve fibre layer (mRNFL), ganglion cell-inner plexiform layer (mGCIPL), outer nuclear layer (ONL), inner segment layer (IS), and outer segment (OS) from macular region OCT scans; arteriolar tortuosity (AT), venular tortuosity (VT), venular width (VW), fractal dimension (FD), vertical cup-to-disc ratio (VCDR), optic cup area (OCA), and optic disc area (ODA) derived from other imaging methods.</p>
RESULTS: There was strong evidence that genetic liability to AD affected the retinal vasculature by specifically increasing AT (β = 0.007;95%CI=0.002,0.011;p-value=0.005) in UK Biobank participants (n=52,798). AD may influence the mRNFL (β=-0.047,95%CI=-0.119,0.023,p-value=0.18) and mGCIPL (β=-0.061;95%CI=-0.14,0.025,p-value=0.16) of the inner retina and OS layer (β = 0.044;95%CI=-0.0001,0.08;p-value=0.05) but the evidence was weak. Multivariable MR analysis showed that a causal relationship between optic disc area and AD (OR=0.76;95%CI=0.62,0.93,p-value=0.009) was probably mediated by refractive error.</p>
CONCLUSION: Early cerebrovascular signs of AD may be detected by examination of the eye. Further investigation is required to determine the clinical utility of eye screening for dementia.</p>
21 Authors
- Humayun Kiser
- Ashley Budu-Aggrey
- Jessica N. Cooke Bailey
- Ana Villaplana-Velasco
- Miguel O. Bernabeu
- Xiaofan Jiang
- Christopher G. Owen
- Jonathan L. Haines
- Louis R. Pasquale
- Stuart MacGregor
- Xiaoyi Raymond Gao
- Janey L. Wiggs
- Chen Jiang
- Hélène Choquet
- International Glaucoma Genetics Consortium NEIGHBORHOOD consortium
- George Davey Smith
- Patrick G. Kehoe
- Neil M. Davies
- Aimee L. Hanson
- Emma L. Anderson
- Denize Atan
1 Application
| Application ID | Title |
|---|---|
| 66267 | Lifestyle and genetics in healthy ageing and dementia |
Enabling scientific discoveries that improve human health