Functional effects of genetic polymorphism in inflammatory genes in subjective memory complainers.
A number of genetic risk factors have been identified for Alzheimer's disease (AD) including genes involved in the inflammatory response (interleukin 1A, [IL-1α (-889)], interleukin 1B (IL-1β [+3953]), and tumor necrosis factor (TNF [-308 and -850]). We investigated the prevalence and functional consequences (baseline cognitive performance, plasma cytokine levels) of possession of these putative genetic risk factors within a group of subjective memory complainers (SMC, n = 226) and age and sex matched noncomplainers (NMC, n = 167). We observed no effect of any of the genetic factors investigated on cognitive performance. Further, there was no difference in the frequency of the disease-associated alleles, or cytokine levels between subjective memory complainers and noncomplainer participants. There was no relationship between TNF polymorphisms and TNF levels. There was a significant increase in plasma IL-1β levels in those homozygous for the disease-associated allele (i.e., IL-1β +3953 TT). Follow-up longitudinal assessments on this cohort will provide insight as to how these polymorphisms may affect the risk of cognitive decline over time.
School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, Western Australia, Australia.
Simon
S
Lau
Kristyn Alissa
KA
Bates
Hamid R
HR
Sohrabi
Mark
M
Rodrigues
Georgia
G
Martins
Satvinder S
SS
Dhaliwal
Kevin
K
Taddei
Simon M
SM
Laws
Ian J
IJ
Martins
Francis L
FL
Mastaglia
Jonathan K
JK
Foster
Jacqueline K
JK
Phillips
Ralph N
RN
Martins
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha