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.
Lau
Simon
S
School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, Western Australia, Australia.
Bates
Kristyn Alissa
KA
Sohrabi
Hamid R
HR
Rodrigues
Mark
M
Martins
Georgia
G
Dhaliwal
Satvinder S
SS
Taddei
Kevin
K
Laws
Simon M
SM
Martins
Ian J
IJ
Mastaglia
Francis L
FL
Foster
Jonathan K
JK
Phillips
Jacqueline K
JK
Martins
Ralph N
RN
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