THE APOLIPOPROTEIN 2 ALLELE IN ALZHEIMER'S DISEASE: SUGGESTIONS FOR A JUDICIOUS USE OF ANTIPLATELET AND ANTICOAGULANT MEDICATIONS

Abstract

To the Editor: Cerebral amyloid angiopathy (CAA) is a common disease in elderly people. It is often unsuspected until it presents as a potentially fatal lobar hemorrhage.1 CAA has a close etiological relationship with Alzheimer's disease (AD); more than 80% of CAA cases occur in the presence of concomitant AD.2 Moreover, 80% to 90% of patients with AD show evidence of CAA on autopsy.3 Although there is deposition of β-amyloid in AD and CAA, the two differ widely with regard to the prognostic significance of apolipoprotein E (ApoE). ApoE2 is a protective factor for AD and is associated with a later age of onset.4 Conversely, ApoE2 is the most important predictor of CAA-related hemorrhage (CAAH);5 in a retrospective study of 36 patients with pathologically confirmed CAAH, subjects were three times as likely as those without to have the ApoE2 genotype.6 In patients with CAA who have the ApoE2 genotype, various clinical factors may further increase the risk of lobar hemorrhages, including minor head trauma, hypertension, and most significantly, the use of antiplatelet and anticoagulant medications.7 A strong synergistic effect was found of the ApoE2 allele and the use of antiplatelet and anticoagulant medications in increasing the risk of CAAH in patients with CAA.8 In another study, which examined the incidence of CAAH secondary to the use of warfarin, it was noticed that patients with the ApoE2 genotype were at a 3.8 times greater risk of developing the hemorrhage.9 The detection of CAA remains a diagnostic challenge, and most cases are clinically silent until they present as a highly lethal lobar hemorrhage. Perhaps the ApoE status of patients with AD could be used to identify the population subset at risk for this serious complication. ApoE testing in patients with AD may help to delineate those at risk for the development of CAAH. Patients with the ApoE2 allele could undergo more-rigorous screening for CAA through susceptibility-weighted imaging. It may still be premature to make any specific recommendations about the use of antiplatelet and anticoagulation medications in patients with AD with the ApoE2 allele, but the high mortality associated with CAAH suggests judicious and cautious clinical use of these medications. Implementing stricter control of blood pressure in these patients may also be a parallel recommendation. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this letter. Author Contributions: Santosh B. Murthy, Ali Jawaid, and Salah U. Qureshi conceived and designed the manuscript, revised the article for intellectual content, and approved the final version for submission. Paul E. Schulz revised the article for intellectual content and approved the final version for submission. Sponsor's Role: None.