Chronic Hypertension Leads to Neurodegeneration in the TgSwDI Mouse Model of Alzheimer’s Disease

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 66; no. 1; pp. 175 - 182
• Main Authors: Kruyer, Anna, Soplop, Nadine, Strickland, Sidney, Norris, Erin H
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.07.2015
• Subjects: Age of Onset; Alzheimer Disease - genetics; Amyloid beta-Peptides - analysis; Amyloid beta-Protein Precursor - genetics; Animals; Blood-Brain Barrier; Brain - blood supply; Cerebral Amyloid Angiopathy - etiology; Cerebral Amyloid Angiopathy - pathology; Chronic Disease; Dementia, Vascular - etiology; Dementia, Vascular - physiopathology; Disease Models, Animal; Female; Hippocampus - pathology; Humans; Hypertension - chemically induced; Hypertension - complications; Hypertension - physiopathology; Male; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microvessels - chemistry; Microvessels - pathology; Mutation; Nerve Degeneration - etiology; Nerve Degeneration - physiopathology; NG-Nitroarginine Methyl Ester - toxicity; Pericytes - pathology; Vasculitis - etiology; Vasculitis - physiopathology; cerebral amyloid angiopathy; hypertension; blood–brain barrier
• DOI: 10.1161/HYPERTENSIONAHA.115.05524
• ISSN: 0194-911X

Numerous epidemiological studies link vascular disorders, such as hypertension, diabetes mellitus, and stroke, with Alzheimer’s disease (AD). Hypertension, specifically, is an important modifiable risk factor for late-onset AD. To examine the link between midlife hypertension and the onset of AD later in life, we chemically induced chronic hypertension in the TgSwDI mouse model of AD in early adulthood. Hypertension accelerated cognitive deficits in the Barnes maze test (P<0.05 after 3 months of treatment; P<0.001 after 6 months), microvascular deposition of β-amyloid (P<0.001 after 3 months of treatment; P<0.05 after 6 months), vascular inflammation (P<0.05 in the dentate gyrus and P<0.001 in the dorsal subiculum after 6 months of treatment), blood–brain barrier leakage (P<0.05 after 3 and 6 months of treatment), and pericyte loss (P<0.05 in the dentate gyrus and P<0.01 in the dorsal subiculum after 6 months of treatment) in these mice. In addition, hypertension induced hippocampal neurodegeneration at an early age in this mouse line (43% reduction in the dorsal subiculum; P<0.05), establishing this as a useful research model of AD with mixed vascular and amyloid pathologies.