Aquaporin-4 polymorphisms predict amyloid burden and clinical outcome in the Alzheimer's disease spectrum

Clearance of amyloid-beta (A beta) from the brain is hypothesized to be mediated by the glymphatic system through aquaporin-4 (AQP4) water channels. Genetic variation of AQP4 may impact water channel function, A beta clearance, and clinical outcomes. We examined whether single-nucleotide polymorphisms (SNPs) of the AQP4 gene were related to A beta neuropathology on [F-18]Florbetapir PET in 100 A beta positive late mild cognitive impairment (LMCI) or Alzheimer's disease (AD) patients and were predictive of clinical outcome in prodromal AD patients. AQP4 SNP rs72878794 was associated with decreased A beta uptake, whereas rs151244 was associated with increased A beta uptake, increased risk of conversion from MCI and LMCI to AD, and an increased 4-year rate of cognitive decline in LMCI. AQP4 genetic variation was associated with A beta accumulation, disease stage progression, and cognitive decline. This variation may correspond to changes in glymphatic system functioning and brain A beta clearance and could be a useful biomarker in predicting disease burden for those on the dementia spectrum. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

The study found that genetic variation of the AQP4 gene is associated with Aβ uptake, neuropathology, clinical outcomes, and cognitive decline, serving as a potential biomarker for predicting disease burden in patients on the dementia spectrum.