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Relationship between severe amyloid angiopathy, apolipoprotein E genotype, and vascular lesions in Alzheimer's
J M Olichney1, L A Hansen, J H Lee
1Alzheimer's Disease Research Center, University of California, San Diego, La Jolla, California 92093-0948, USA. olichney@cogsci.ucsd.edu
Insights
Cerebral amyloid angiopathy (CAA) is linked to cerebrovascular lesions (VLs) in Alzheimer's disease (AD). Severe CAA contributes to VLs independently of apolipoprotein E (ApoE) genotype, suggesting a direct pathogenic role.
Area of Science:
- Neurology
- Neuroscience
- Pathology
Background:
- Cerebral amyloid angiopathy (CAA) is a significant factor in Alzheimer's disease (AD) pathology.
- CAA is associated with various cerebrovascular lesions (VLs), including lobar hemorrhages, small infarcts, and microinfarcts.
- Apolipoprotein E4 (ApoE4) is a major genetic risk factor for AD and may predispose individuals to CAA and cerebrovascular disease.
Purpose of the Study:
- To elucidate the intricate relationship between CAA, ApoE, and VLs in AD.
- To review evidence supporting CAA as a cause of specific VLs.
- To examine the role of ApoE4 in CAA and cerebrovascular disease.
Main Methods:
- Review of existing scientific literature and evidence.
- Analysis of patient data stratified by ApoE genotype.
- Examination of the association between CAA severity and VLs.
Main Results:
- CAA is strongly associated with and may cause lobar hemorrhages, small infarcts, and microinfarcts.
- ApoE4 influences susceptibility to CAA and cerebrovascular disease.
- VLs increase with severe CAA, even within homogenous ApoE genotype groups (E4/4 and E3/3).
Conclusions:
- The link between CAA and VLs is not solely due to ApoE genotype variations.
- Severe CAA plays a direct pathogenic role in the development of many VLs observed in AD.
- Understanding this relationship is crucial for AD pathogenesis and therapeutic strategies.
Abstract:
In this brief review, we aim to describe the complex relationship between cerebral amyloid angiopathy (CAA), apolipoprotein E (ApoE), and cerebrovascular lesions in Alzheimer's disease (AD). First, we review the evidence that CAA is associated with, and may cause, specific types of vascular lesions (VLs). In addition to being a leading cause of lobar hemorrhages in the elderly, CAA has been implicated as a likely cause of small infarcts, microinfarcts, and incomplete infarctions in the deep white matter. We also review the role that ApoE4 (the major genetic risk factor for AD) has in predisposing toward CAA, coronary artery disease, and possibly toward cerebrovascular disease. Last, we provide evidence that the association between CAA and VLs is not a spurious one due to an increase in the ApoE4 genotype. Even within patient groups with the same ApoE genotype (specifically, E4/4 homozygotes and E3/3 homozygotes), our recent analyses have found significant increases in VLs in association with severe CAA. We discuss the implications of this finding as advancing a pathogenic role for severe CAA in producing many of the VLs commonly found in AD cases.