HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hayes, A Articles by Mann, D M A Search for Related Content PubMed PubMed Citation Articles by Hayes, A Articles by Mann, D M A Related Collections Neuropathology Other immunology Genetics Dementia

A polymorphic variation in the interleukin 1A gene increases brain microglial cell activity in Alzheimer’s disease

¹ Neuroscience Research Group, University of Manchester, Greater Manchester Neurosciences Centre, Hope Hospital, Manchester M6 8HD, UK
² Molecular Psychiatry Department, Division of Neuroscience, Queen Elizabeth Psychiatry Hospital, University of Birmingham, Birmingham B15 2QZ, UK
³ INSERM 508, Institut Pasteur de Lille, 59019 Lille Cedex, France
⁴ Department of Old Age Psychiatry, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK

Correspondence to:
Correspondence to:
Professor D M A Mann
Neuroscience Research Group, University of Manchester, Greater Manchester Neurosciences Centre, Hope Hospital, Salford M6 8HD, UK; david.mann{at}man.ac.uk

ABSTRACT
Objective: To investigate the impact of possession of the –889 C/T polymorphism of the interleukin 1A gene (IL-1A) and the –511 C/T polymorphism of the interleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alzheimer’s disease (AD), as demonstrated by the degree of microglial cell activity associated with each IL-1A and IL-1B genotype.

Method: Microglial cell activity within the frontal cortex was determined in 68 patients with necropsy confirmed AD by image analysis as the percentage area of tissue occupied by ferritin immunostained material (microglial cell load). IL-1A, IL-1B, and apolipoprotein E (APOE) genotyping were performed by polymerase chain reaction on DNA extracted from frontal cortex or cerebellum.

Results: The microglial cell load was 31% greater in patients with IL-1A T allele, 62% greater with IL-1A TT genotype, but 108% greater with IL-1A TT genotype in combination with APOE 4 allele. No effects on microglial cell load occurred with polymorphisms in IL-1B, or APOE alone.

Conclusions: Polymorphisms within IL-1A influence the degree of brain microglial cell activation, especially in bearers of APOE 4 allele, reinforcing the importance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.

Abbreviations: Aß, amyloid ß; AD, Alzheimer’s disease; APOE, apolipoprotein E; IL, interleukin

Keywords: Alzheimer’s disease; interleukin 1; microglial cells; neuroinflammation