title: Apolipoprotein E and Sex Bias in Cerebrovascular Aging of Men and Mice.
abstract: Alzheimer disease (AD) research has mainly focused on neurodegenerative processes associated with the classic neuropathologic markers of senile plaques and neurofibrillary tangles. Additionally, cerebrovascular contributions to dementia are increasingly recognized, particularly from cerebral small vessel disease (SVD). Remarkably, in AD brains, the apolipoprotein E (ApoE) ɛ4 allele shows male excess for cerebral microbleeds (CMBs), a marker of SVD, which is opposite to the female excess of plaques and tangles. Mouse transgenic models add further complexities to sex-ApoE ɛ4 allele interactions, with female excess of both CMBs and brain amyloid. We conclude that brain aging and AD pathogenesis cannot be understood in humans without addressing major gaps in the extent of sex differences in cerebrovascular pathology.
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Department of Biological Sciences, Dornsife College, University of Southern California, Los Angeles, CA, USA. Electronic address: cefinch@usc.edu.
authors.forename: Caleb E
authors.initials: CE
authors.lastname: Finch
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Radiology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: sara.shams@ki.se.
authors.forename: Sara
authors.initials: S
authors.lastname: Shams
mesh_terms: D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012727:Sex Characteristics
chemical_list: D001057:Apolipoproteins E; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C579624:apolipoprotein E (133-149)
keywords: apolipoprotein E; cerebral amyloid angiopathy; cerebral microbleeds; cerebrovasculature; magnetic resonance imaging; sex; small vessel disease