Clinical studyPrevalence of cerebral vascular amyloid-β deposition and stroke in an aging Australian population: a postmortem study
Introduction
Cerebral amyloid angiopathy (CAA) is recognised as a cause of spontaneous lobar haemorrhage in the elderly and as a risk factor for anticoagulant-induced cerebral haemorrhage.[1], [2], [3], [4], [5], [6] However, it is not known what proportion of individuals with CAA suffer a cerebral haemorrhage. It has also been suggested that CAA is a risk factor for ischaemic stroke, but the evidence for this is less conclusive.[7], [8] Pathological studies have shown that CAA may also be associated with the development of cerebral microhaemorrhages, microinfarcts and leukoencephalopathy.[3], [8], [9], [10] Familial forms of CAA due to mutations in the β-amyloid precursor protein and cystatin C genes are associated with recurrent intracerebral haemorrhage, as well as ischaemic stroke and dementia, with onset as early as the third decade of life.[11], [12], [13] Recent studies have suggested that the apolipoprotein ε4 allele is a risk factor for sporadic CAA,[14], [15], [16], [17] and that the severity of CAA in the elderly may be influenced by the presence of an intronic polymorphism in the presenilin-1 gene.18
Previous autopsy studies have shown that the prevalence of sporadic CAA, as determined by staining with the Congo-red technique, is age-dependent and that the prevalence increases particularly over the age of 70 years.[2], [4], [19], [20] However, this increase has not been found in all studies,21 and the age-adjusted prevalence has varied in studies from different countries, suggesting that racial factors may play a part in determining susceptibility to CAA.
Amyloid-β (Aβ) is the principal component of vascular amyloid and the major protein that accumulates in cerebral blood vessels and in the brain parenchyma in Alzheimer’s disease and with aging.[22], [23], [24] While Aβ usually accumulates both in the cerebral blood vessels and in the brain parenchyma as amyloid plaques, in some cases there is predominantly vascular Aβ deposition and it has been suggested that such cases may represent a microvascular variant of Alzheimer’s disease.25 It is not known whether there are differences in the prevalence and age at onset of vascular and parenchymal Aβ deposition in the cortex with aging.
The aims of the present study were to compare the prevalence of vascular and parenchymal Aβ deposition in the cerebral cortex at postmortem in an aging Australian population, and to determine whether, in the population studied, there is an association between vascular Aβ deposition and cerebral haemorrhage or infarction.
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Materials and methods
The study group comprised 100 consecutive cases over a 2 year period from the files of the Department of Neuropathology, of individuals aged 50–91 years (40 females; mean age 75.1 years) not known to be demented or to have a neurological disorder, who died unexpectedly and in whom a Coroner’s postmortem was performed to establish the cause of death. The major causes of death were ischaemic heart disease, trauma and suicide. Brains were examined after formalin fixation and were sectioned using a
A deposition
As shown in Table 2, Table 3, vascular Aβ deposition was first found in the 7th decade and the proportion of brains with vascular Aβ increased to a maximum of 48% in the 9th decade. In 77% of brains with vascular Aβ there was also parenchymal Aβ deposition, while in 23% there was vascular involvement only. Parenchymal Aβ was first found in the 6th decade and had a higher prevalence than vascular Aβ, the proportion of positive brains increasing to a maximum of 64% in the 9th decade. Kaplan–Meier
Discussion
Our findings indicate that, in the population studied, the prevalence of vascular Aβ deposition in the cerebral cortex was age-dependent, occurring first in the 7th decade, and increasing progressively in the 8th and 9th decades as was also found in previous postmortem studies of CCA from Japan and Canada.[2], [19], [20] However, our figures differ from those reported by Esiri and Wilcock21 in a study from the UK who did not find an increase in prevalence of CAA after the 7th decade in a
Acknowledgements
We thank the pathologists who performed the postmortem examinations; Dr L Davies who contributed to the collection of the brain specimens; Professor C Masters and Professor K Beyreuther who kindly provided the amyloid-β antibody; Professor G Hammond for statistical assistance; and Mrs S Moncrieff for expert secretarial assistance.
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