Title |
The role of APOE in cerebrovascular dysfunction
|
---|---|
Published in |
Acta Neuropathologica, February 2016
|
DOI | 10.1007/s00401-016-1547-z |
Pubmed ID | |
Authors |
Leon M. Tai, Riya Thomas, Felecia M. Marottoli, Kevin P. Koster, Takahisa Kanekiyo, Alan W. J. Morris, Guojun Bu |
Abstract |
The ε4 allele of the apolipoprotein E gene (APOE4) is associated with cognitive decline during aging, is the greatest genetic risk factor for Alzheimer's disease and has links to other neurodegenerative conditions that affect cognition. Increasing evidence indicates that APOE genotypes differentially modulate the function of the cerebrovasculature (CV), with apoE and its receptors expressed by different cell types at the CV interface (astrocytes, pericytes, smooth muscle cells, brain endothelial cells). However, research on the role of apoE in CV dysfunction has not advanced as quickly as other apoE-modulated pathways. This review will assess what aspects of the CV are modulated by APOE genotypes during aging and under disease states, discuss potential mechanisms, and summarize the therapeutic significance of the topic. We propose that APOE4 induces CV dysfunction through direct signaling at the CV, and indirectly via modulation of peripheral and central pathways. Further, that APOE4 predisposes the CV to damage by, and exacerbates the effects of, additional risk factors (such as sex, hypertension, and diabetes). ApoE4-induced detrimental CV changes include reduced cerebral blood flow (CBF), modified neuron-CBF coupling, increased blood-brain barrier leakiness, cerebral amyloid angiopathy, hemorrhages and disrupted transport of nutrients and toxins. The apoE4-induced detrimental changes may be linked to pericyte migration/activation, astrocyte activation, smooth muscle cell damage, basement membrane degradation and alterations in brain endothelial cells. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Canada | 2 | <1% |
United Kingdom | 1 | <1% |
Poland | 1 | <1% |
United States | 1 | <1% |
Unknown | 210 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 38 | 18% |
Researcher | 31 | 14% |
Student > Master | 20 | 9% |
Student > Doctoral Student | 15 | 7% |
Student > Bachelor | 15 | 7% |
Other | 31 | 14% |
Unknown | 65 | 30% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 48 | 22% |
Medicine and Dentistry | 27 | 13% |
Agricultural and Biological Sciences | 19 | 9% |
Psychology | 12 | 6% |
Biochemistry, Genetics and Molecular Biology | 10 | 5% |
Other | 24 | 11% |
Unknown | 75 | 35% |