A polymorphism of the interleukin-1 beta gene at position +3953 influences progression and neuro-pathological hallmarks of Alzheimer’s disease

• Published in: Neurobiology of aging 2004-09, Vol.25 (8), p.1017-1022
• Main Authors: Licastro, Federico, Veglia, Fabrizio, Chiappelli, Martina, Grimaldi, Luigi Maria E, Masliah, Eliezer
• Format: Article
• Language: English
• Subjects: Age of Onset; Aged; Alzheimer Disease - genetics; Alzheimer Disease - immunology; Alzheimer Disease - pathology; Alzheimer’s disease; APOE ε; Apolipoprotein E4; Apolipoproteins E - genetics; Biological and medical sciences; Brain - immunology; Brain - metabolism; Brain - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; DNA Mutational Analysis; Encephalitis - genetics; Encephalitis - immunology; Encephalitis - pathology; Female; Genetic Predisposition to Disease - genetics; Genetic Testing; Humans; IL-β genes; Interleukin-1 - genetics; Interleukin-1 - immunology; Male; Medical sciences; Neurofibrillary Tangles - genetics; Neurofibrillary Tangles - immunology; Neurofibrillary Tangles - pathology; Neurology; Neuropathology; Plaque, Amyloid - genetics; Plaque, Amyloid - immunology; Plaque, Amyloid - pathology; Point Mutation - genetics; Polymorphism, Genetic - genetics; Survival Rate
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2003.11.002

Interleukin-1 (IL-1) gene polymorphisms are associated with an increased risk of Alzheimer’s disease (AD) and it has been suggested that altered immune responses of the brain may play a role in the pathogenesis of the disease. Here we investigated whether IL-1β polymorphisms affected neuro-pathological features and clinical status of AD patients with autopsy confirmed diagnosis of the disease. AD patients ( n=133) were genotyped for the polymorphic regions in the apolipoprotein E ε (APOE ε) and interleukin-1β (IL-1β)) genes. APOE ε4 carriers showed increased neuritic amyloid plaques (NP) and neurofibrillary tangles (NFT). The IL-1β +3953 polymorphism influenced survival in AD patients and those with the TT genotype and without the APOE ε4 allele showed the shortest cumulative survival. Patients with the +3953 IL-1β T and without the APOE ε4 alleles had reduced NP and NFT, a delayed ages at onset and death, but a decreased duration of the disease. On the other hand a different polymorphism of the IL-1β gene at position −511 did not influence any AD features. Our findings suggest that IL-1β gene by affecting brain immune responses may influence the age at onset of the disease, survival and AD progression.