title: Assessment of activation of the plasma kallikrein-kinin system in frontal and temporal cortex in Alzheimer's disease and vascular dementia.
abstract: Decreased cerebral blood flow and blood-brain barrier disruption are features of Alzheimer's disease (AD). The plasma kallikrein-kinin system modulates cerebrovascular tone through release of vasoactive bradykinin (BK). Cerebroventricular infusion of Aβ1-40 enhances BK release, suggesting that the activity of this system may be elevated in AD. We investigated the profile of the activating protease of this system, plasma kallikrein (PK), in frontal and temporal brain tissue from postmortem confirmed cases of AD, vascular dementia (VaD), and controls. Measurements of neuron specific enolase messenger ribonucleic acid (mRNA) and protein were used to adjust for neuronal loss. Adjusted PK mRNA was significantly increased in the frontal cortex in AD, and the frontal and temporal cortex in VaD. Similar trends were seen for PK protein level in AD and VaD. PK activity was significantly increased in the frontal and temporal cortex in AD. Increased PK activity in AD is likely to contribute to increased BK release and may thereby influence cerebral blood flow and vascular permeability.
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Ashby
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D001920:Bradykinin / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D015140:Dementia, Vascular / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007610:Kallikreins / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013702:Temporal Lobe / Q000201:enzymology / Q000378:metabolism*
chemical_list: D007610:Kallikreins; D001920:Bradykinin