Chronic Hypertension Leads to Neurodegeneration in the TgSwDI Mouse Model of Alzheimer's Disease.
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.
From the Patricia and John Rosenwald Laboratory of Neurobiology and Genetics (A.K., S.S., E.H.N.), Electron Microscopy Resource Center (N.S.), The Rockefeller University, New York, NY.
Anna
A
Kruyer
From the Patricia and John Rosenwald Laboratory of Neurobiology and Genetics (A.K., S.S., E.H.N.), Electron Microscopy Resource Center (N.S.), The Rockefeller University, New York, NY.
Nadine
N
Soplop
From the Patricia and John Rosenwald Laboratory of Neurobiology and Genetics (A.K., S.S., E.H.N.), Electron Microscopy Resource Center (N.S.), The Rockefeller University, New York, NY.
Sidney
S
Strickland
From the Patricia and John Rosenwald Laboratory of Neurobiology and Genetics (A.K., S.S., E.H.N.), Electron Microscopy Resource Center (N.S.), The Rockefeller University, New York, NY. enorris@rockefeller.edu.
Erin H
EH
Norris
D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000032:analysis; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply; D016657:Cerebral Amyloid Angiopathy / Q000209:etiology / Q000473:pathology; D002908:Chronic Disease; D015140:Dementia, Vascular / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055806:Microvessels / Q000737:chemistry / Q000473:pathology; D009154:Mutation; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D009410:Nerve Degeneration / Q000209:etiology* / Q000503:physiopathology; D020286:Pericytes / Q000473:pathology; D014657:Vasculitis / Q000209:etiology / Q000503:physiopathology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019331:NG-Nitroarginine Methyl Ester
blood–brain barrier; cerebral amyloid angiopathy; hypertension