title: Common Impact of Chronic Kidney Disease and Brain Microhemorrhages on Cerebral Aβ Pathology in SHRSP.
abstract: While chronic kidney disease seems to be an independent risk factor for cognitive decline, its impact on cerebral amyloid-β (Aβ) depositions, one hallmark of Alzheimer's Disease (AD) pathology, has not been investigated. Utilizing 80 male nontransgenic spontaneously hypertensive stroke prone rats (SHRSP) at various ages (12 to 44 weeks), tubulointerstitial renal damage, prevalence of cerebral microhemorrhages and Aβ accumulations were quantified. Using age-adjusted general linear models we investigated the main and interaction effects of renal damage and cerebral microhemorrhages on cerebral Aβ load. In addition, using post mortem human brain tissue of 16 stroke patients we examined the co-localization of perivascular Aβ deposits and small vessel wall damage. Statistical models revealed an age-independent main effect of tubulointerstitial kidney damage on brain Aβ accumulations, which was reinforced by the consecutive presence of cerebral microhemorrhages. Moreover, cerebral microhemorrhages independently predicted brain Aβ burden in SHRSP. In up to 69% of all human cases perivascular Aβ deposits were detected in the direct vicinity of small vessel wall damage. Our results support the associations between vascular pathology and Aβ deposition, and demonstrate a relationship between chronic kidney disease and cerebral Aβ pathology. Hence, our data suggest that prevention of chronic renal damage may reduce cerebral Aβ pathology.
authors.affiliation: Department of Research Methodology, University of Medicine and Pharmacy of Craiova, Petru Rares Street 2, Craiova, 200349, Romania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pirici
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, Magdeburg, 39120, Germany.|Mossakowski Medical Research Centre PAS, Pawińskiego 5, Warsaw, 02-106, Poland.
authors.forename: Luiza
authors.initials: L
authors.lastname: Stanaszek
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, Magdeburg, 39120, Germany.|Department of Neurology, Otto-von-Guericke University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Garz
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, Magdeburg, 39120, Germany.|Department of Neurology, Otto-von-Guericke University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Solveig
authors.initials: S
authors.lastname: Niklass
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, Magdeburg, 39120, Germany.|Department of Neurology, Otto-von-Guericke University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.affiliation: Department of Pathology, Otto-von-Guericke University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kalinski
authors.affiliation: Campus for Ageing and Vitality, Institute of Neuroscience and Newcastle University Institute for Ageing, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, Magdeburg, 39120, Germany.|Department of Neurology, Otto-von-Guericke University, Leipziger Strasse 44, Magdeburg, 39120, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000473:pathology; D059345:Cerebral Small Vessel Diseases / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides
keywords: SHRSP; amyloid β; cerebral small vessel disease; chronic kidney disease; microhemorrhages; two hit vascular hypothesis of AD