Cerebral amyloid angiopathy in traumatic brain injury: association with apolipoprotein E genotype
- 1Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College London, London, UK
- 2University Academic Unit of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK
- 3Neuropathology Lab., Department of Pathology, University of Edinburgh, Western General Hospital, Edinburgh, UK
- 4Clinical Neurosciences, University of Southampton, Southampton General Hospital, Southampton, UK
- Correspondence to: Dr S M Gentleman Division of Neuroscience and Psychological Medicine, Imperial College London, Charing Cross Campus, St Dunstan’s Road, London W6 8RP, UK;
- Received 9 October 2003
- Accepted 24 May 2004
- Revised 19 May 2004
Objective: In view of the association of the apolipoprotein E (APOE) ε4 allele with poor outcome after traumatic brain injury we determined the frequency of cerebral amyloid angiopathy (CAA) and the extent of haemorrhagic pathology in relation to APOE genotype in an autopsy series of 88 head injured cases.
Methods: Tissue sections from the frontal and temporal lobes were immunostained for amyloid-β peptide (Aβ) and stained for Congo red to identify vascular amyloid pathology. A semiquantitative assessment of contusions, the total contusion index, was used to estimate the severity of the haemorrhagic pathology. APOE genotypes were determined by polymerase chain reaction of genomic DNA extracted from paraffin embedded tissue sections.
Results: CAA was present in 7/40 (18%) ε4 carriers compared with 1/48 (2%) non-ε4 carriers (p = 0.021, 95% confidence interval (CI) for difference in proportions with CAA 3% to 29%) with 6/40 (4 with CAA) ε4 carriers being homozygotes. Thus the risk of having CAA for ε4 carriers was 8.4 times that for the non-ε4 carriers. However, there was no clear tendency for patients with CAA to have more severe or more numerous contusions (median contusion index 19 (CAA) v 14.5, p = 0.23, 95% CI for difference in medians −5 to 14).
Conclusions: Presence of CAA in head injured cases was significantly associated with possession of an APOE ε4 allele but not with the severity of contusions.
This study was funded in part by grants from the Medical Research Council (G9814486) and National Institute of Health (AG12411).
Competing interests: JARN and DIG are named applicants on the following patent: Method of prognosing chronic neurodegenerative pathology following a head injury. UK patent application 9415073.7 filed jointly by SmithKline Beecham and University of Glasgow on 27 July 1994; PCT worldwide application PCT/EP95/02827 filed on 13 July 1995; awarded 5 May 1998 (US5747260).