Variants in Neurotransmitter-Related Genes Are Associated with Alzheimer’s Disease Risk and Cognitive Functioning but Not Short-Term Treatment Response

TL;DR

This study finds some genetic variants linked to Alzheimer's risk and cognitive function in Mexican patients, but no genetic factors affect treatment response.

Contribution

The study identifies novel genetic associations with Alzheimer's disease risk in an admixed Mexican population.

Findings

Variants in ABCB1, ACHE, and CHAT are associated with Alzheimer's disease risk.

BCHE rs1803274 is linked to worse cognitive functioning.

No genetic or non-genetic factors influence short-term treatment response to ChEIs or memantine.

Abstract

Background/Objectives: Several genetic factors are related to the risk of Alzheimer’s disease (AD) and the response to cholinesterase inhibitors (ChEIs) (donepezil, galantamine, and rivastigmine) or memantine. However, findings have been controversial, and, to the best of our knowledge, admixed populations have not been previously evaluated. We aimed to determine the impact of genetic and non-genetic factors on the risk of AD and the short-term response to ChEIs and memantine in patients with AD from Mexico. Methods: This study included 117 patients from two specialty hospitals in Mexico City, Mexico. We evaluated cognitive performance via clinical evaluations and neuropsychological tests. Nineteen variants in ABCB1, ACHE, APOE, BCHE, CHAT, CYP2D6, CYP3A5, CHRNA7, NR1I2, and POR were assessed through TaqMan assays or PCR. Results: Minor alleles of the ABCB1 rs1045642, ACHE rs17884589, and CHAT rs2177370 and rs3793790 variants were associated with the risk of AD; meanwhile, CHRNA7 rs6494223 and CYP3A5 rs776746 were identified as low-risk variants in AD. BCHE rs1803274 was associated with worse cognitive functioning. None of the genetic and non-genetic factors studied were associated with the response to pharmacological treatment. Conclusions: We identified potential genetic variants related to the risk of AD; meanwhile, no factor was observed to impact the response to pharmacological therapy in patients with AD from Mexico.

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