Your GLP-1 and GIP Receptor Genes May Affect Whether You Develop Alzheimer's or Parkinson's Disease | Research

The takeaway

Genetic variants in GLP-1 receptor (GLP1R) and GIP receptor (GIPR) genes were associated with increased risk of Alzheimer's and Parkinson's disease, and with Alzheimer's CSF biomarkers and dementia in Parkinson's patients.

OR 1.95 for PD dementia
GIPR rs1800437 C allele carriers had nearly doubled odds of developing dementia in Parkinson's disease

What the researchers found

GLP1R rs10305420 genotype was associated with increased odds of both AD and PD, GLP1R variants correlated with AD CSF biomarkers, and GIPR rs1800437 was associated with dementia development in PD (OR 1.95).

Why it matters

This is genetic evidence that the same receptor systems targeted by blockbuster diabetes drugs play a role in neurodegeneration. Patients with specific GLP1R/GIPR variants may be at higher neurodegenerative risk — and potentially better candidates for GLP-1/GIP drug neuroprotection.

The numbers in context

AD and PD patients studied; GLP1R and GIPR genetic variability assessed in relation to disease phenotypes.

How the study worked

Case-control genetic study. AD patients, PD patients, and healthy controls genotyped for GLP1R rs10305420, GLP1R rs6923761, and GIPR rs1800437. CSF biomarkers measured in AD; cognitive function assessed in PD.

Who was studied

Patients with Alzheimer's disease and Parkinson's disease

What this study cannot tell us

Observational genetic association study — cannot prove causation. Sample sizes not specified in abstract. Population-specific genetic frequencies may limit generalizability. Functional impact of these SNPs on receptor signaling not directly assessed.

How to read the evidence

Moderate evidence — genetic association study with disease-relevant biomarker correlations. Replication in independent cohorts needed.

When this study was published

Published in 2024. Adds genetic support to the growing GLP-1/neurodegeneration hypothesis.

The bigger picture

Pharmacogenomics could personalize GLP-1/GIP therapy for neurodegeneration. If certain genetic variants predict both disease risk and drug response, genotyping could guide which patients receive GLP-1/GIP drugs for neuroprotection — a precision medicine approach to dementia prevention.

Questions still open

Do patients with GLP1R risk variants respond differently to GLP-1 agonist neuroprotective treatment?
Should GLP1R/GIPR genotyping be included in Alzheimer's risk assessment panels?
Do these genetic variants affect GLP-1/GIP drug efficacy for diabetes treatment as well?

Common questions

Can your genes affect whether diabetes drugs might protect your brain?

This study found that specific variations in the genes for GLP-1 and GIP receptors — the same receptors targeted by drugs like Ozempic and tirzepatide — are linked to higher risk of Alzheimer's and Parkinson's disease. This suggests these receptors play a role in brain health, and the genetic variations might help identify who would benefit most from these drugs for brain protection.

Does having diabetes increase Alzheimer's risk?

Research increasingly suggests a connection. This study found that genetic variations in the receptors for diabetes-related hormones (GLP-1 and GIP) are linked to both Alzheimer's and Parkinson's risk. This supports the theory that insulin signaling pathways in the brain contribute to neurodegeneration — and that diabetes drugs targeting these pathways might offer neuroprotection.

Read the original research

Genetic variability of incretin receptors affects the occurrence of neurodegenerative diseases and their characteristics.

Heliyon, 10(20), e39157

View on PubMed ↗Publisher’s paper ↗

Citation

Vogrinc, David; Redenšek Trampuž, Sara; Blagus, Tanja; Trošt, Maja; Gregorič Kramberger, Milica; Emeršič, Andreja; Čučnik, Saša; Goričar, Katja; Dolžan, Vita. (2024). Genetic variability of incretin receptors affects the occurrence of neurodegenerative diseases and their characteristics.. Heliyon, 10(20), e39157. https://doi.org/10.1016/j.heliyon.2024.e39157