Apolipoprotein E epsilon 4 allele frequency in vascular dementia and Alzheimer's disease.

Abstract

of aspirin and ticlopidine before continuing long-term treatment. Our patients, however, were homogeneous in terms of infarct size and clinical severity.As Dr Ozturk and colleagues state, further studies based on a large number of patients (with more appropriate controls) are necessary to determine the significance of the coagulation-fibrinorysis markers for stroke and stroke recurrence and the effects of antiplatelet medication on the markers. Apolipoprotein E c4 Allele Frequency in Vascular Dementia and Alzheimer's DiseaseTo the Editor The issue of apolipoprotein E (apo E) polymorphism has been receiving a great deal of attention in the neurological literature.13 It has been suggested in Stroke that the frequent e3/£4 phenotype may protect against vascular morbidity 2 and that the e4 allele might be a predisposing genetic marker for ischemic cerebrovascular disease. 1 However, the «4 allele has recently been reported to also be more frequent in patients with sporadic Alzheimer's disease (40% in patients with Alzheimer's disease compared with 10% to 16% of control subjects), 1 -3 -4 raising questions about the specificity of €4 as a risk factor for cerebrovascular or Alzheimer's disease. 3 We assessed apo E allele frequencies in 51 elderly control subjects, 23 subjects with vascular dementia, 6 and 93 patients with Alzheimer's disease. Apo E phenotype was determined by isoelectric focusing in immobilized pH gradients and immunodetection by sheep anti-apo E antibodies. Frequency of the e4 allele is higher in both patients with vascular dementia and those with Alzheimer's disease than in age-matched control subjects or a younger Italian population 7 (Table).The association of the apo E allele with vascular disease has been repeatedly reported, 1 and it should not be surprising that it appears more frequently in patients with vascular dementia than in control subjects. However, this casts doubt on its specificity as a risk factor for Alzheimer's disease.A unifying explanation of the association of the e4 allele with both vascular dementia and Alzheimer's disease might involve the role of apo E isoforms in the repair processes in the nervous system. Apo E is synthesized in the central nervous system and plays a role in normal brain lipid metabolism.

Vascular Dementia

“…[42][43][44][45][46] This raises the possibility that this allele is not a specific marker for AD but is associated with the repair processes in the nervous system. 47 Given that APOE plays a role in normal brain metabolism, it can be hypothesized-as suggested by Frisoni et al 42 -that different insults, either degenerative or vascular, might result in greater damage when ⑀4 allele is present. However, since the diagnosis of pure VaD is only probable according to the NINDS-AIREN criteria, co-occurrence of AD is possible and may explain part of the association with APOE.…”

White Matter Changes and Poststroke Dementia

“…The frequent association of prestroke dementia with hippocampal atrophy pleads for AD [62]. AD and stroke have common genetic risk factors such as the Â4 allele of the apolipoprotein E gene [63]. Moreover, several data suggest that AD patients have some degree of vascular changes: cerebral amyloid angiopathy [8,64], non-specific fibrohyaline thickening of the wall of the small perforating intracerebral arteries [18,65] and increased common intima-media thickness in the common carotid artery [66].…”

Epidemiology of Vascular Dementia

“…The Â4 allele of the apolipoprotein E gene (APOE) is associated with a higher risk of ischemic stroke or coronary heart diseases [134][135][136]. The APOE Â4 allele has also been firmly established as a major risk factor for late-onset AD [137][138][139]. These findings suggest pathogenic relationships between cerebral ischemia and AD [140].…”