Roles of Apolipoprotein E in Alzheimer’s Disease and Other Neurological Disorders

By P. Verghese, Joseph M. Castellano, D. Holtzman. Lancet Neurology, 2011

821 citations recorded by the source corpus.

Summary Apolipoprotein E (ApoE) is a 299 amino acid protein encoded by the APOE gene. Three common polymorphisms in the APOE gene, ε2, ε3, and ε4, result in single amino changes in the ApoE protein. The APOEε2, ε3, and ε4 alleles strongly and dose-dependently alter the likelihood of developing Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). In particular, APOE ε4 is associated with increased risk for AD, whereas APOEε2 is associated with decreased risk. The effects of APOE genotype on AD and CAA risk are likely mediated, in large part, by differential effects of the ApoE protein on amyloid-β (Aβ) accumulation in the brain and cerebrovasculature. Recent data indicate that responses to AD treatments may differ according to APOE genotype. The APOE ε4 allele is also associated with poor outcome following traumatic brain injury and brain hemorrhage, though the mechanisms underlying these associations are unclear. Given the convincing body of literature tying APOE genotype to AD and CAA risk, APOE has also been studied in relation to other neurological diseases. While the possibility that APOE plays a role in these diseases is of great interest, convincing associations have not yet emerged.

Subfields: Molecular Biology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/f681e697aba8f9dcbdda94d6b7c2607ebf82e23c

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Citations in the corpus

Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders (2011, background): “Importantly, a recent longitudinal CBF study in neurologically normal individuals revealed that people bearing the apolipoprotein E (APOE) ɛ 4 allele — the major genetic risk factor for late-onset Alzheimer's diseas”
Recent advances in Alzheimer’s disease: mechanisms, clinical trials and new drug development strategies (2024, background): “118 Research indicates that APOE protein is detectable in neuritic plaques, and individuals with the APOE ε 4 allele also have a higher burden of A β plaques in their brains, 119,120 highlighting its critical in ﬂ uences on A β deposition.”
The neuropathological diagnosis of Alzheimer’s disease (2019, background): “Furthermore, APOE4 allele appears to confer risk for vascular dementia, Lewy body dementia, Down’s syndrome and traumatic brain injury [15].”
Human apoE isoforms differentially regulate brain amyloid-β peptide clearance (2011, neutral): “Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40).”
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “APOE ε4 affects AD risk and age of onset dose dependently [452, 454].”
Post-stroke cognitive impairment: epidemiology, mechanisms and management. (2014, background): “Besides that, the risk gene of AD, APOE ε4, is related to the poor cognitive outcome after stroke (78).”
Alzheimer's disease (2018, background): “for sporadic AD: compared to non-e4 carriers, e4 heterozygotes have an odds ratio (OR) for AD of ~3, rising to ~12 in homozygotes [7].”
The pathobiology of vascular dementia (2013, neutral): “The ApoE 4 allele is a well-established susceptibility gene for increased cardiovascular risk and Alzheimer disease (Verghese et al., 2011).”
Microglial cell origin and phenotypes in health and disease (2011, background): “Other important genetic factors, such as polymorphisms in the genes encoding apolipoprotein E and tau, were also reported to be involved in the activation of microglia and are reviewed elsewher”