TY - JOUR
T1 - Immunotherapy of cerebrovascular amyloidosis in a transgenic mouse model
AU - Lifshitz, Veronica
AU - Weiss, Ronen
AU - Benromano, Tali
AU - Kfir, Einat
AU - Blumenfeld-Katzir, Tamar
AU - Tempel-Brami, Catherine
AU - Assaf, Yaniv
AU - Xia, Weiming
AU - Wyss-Coray, Tony
AU - Weiner, Howard L.
AU - Frenkel, Dan
PY - 2012/2
Y1 - 2012/2
N2 - Cerebrovascular amyloidosis is caused by amyloid accumulation in walls of blood vessel walls leading to hemorrhagic stroke and cognitive impairment. Transforming growth factor-β1 (TGF-β1) expression levels correlate with the degree of cerebrovascular amyloid deposition in Alzheimer's disease (AD) and TGF-β1 immunoreactivity in such cases is increased along the cerebral blood vessels. Here we show that a nasally administered proteosome-based adjuvant activates macrophages and decreases vascular amyloid in TGF-β1 mice. Animals were nasally treated with a proteosome-based adjuvant on a weekly basis for 3 months beginning at age 13 months. Using magnetic resonance imaging (MRI) we found that while control animals showed a significant cerebrovascular pathology, proteosome-based adjuvant prevents further brain damage and prevents pathological changes in the blood-brain barrier. Using an object recognition test and Y-maze, we found significant improvement in cognition in the treated group. Our findings support the potential use of a macrophage immunomodulator as a novel approach to reduce cerebrovascular amyloid, prevent microhemorrhage, and improve cognition.
AB - Cerebrovascular amyloidosis is caused by amyloid accumulation in walls of blood vessel walls leading to hemorrhagic stroke and cognitive impairment. Transforming growth factor-β1 (TGF-β1) expression levels correlate with the degree of cerebrovascular amyloid deposition in Alzheimer's disease (AD) and TGF-β1 immunoreactivity in such cases is increased along the cerebral blood vessels. Here we show that a nasally administered proteosome-based adjuvant activates macrophages and decreases vascular amyloid in TGF-β1 mice. Animals were nasally treated with a proteosome-based adjuvant on a weekly basis for 3 months beginning at age 13 months. Using magnetic resonance imaging (MRI) we found that while control animals showed a significant cerebrovascular pathology, proteosome-based adjuvant prevents further brain damage and prevents pathological changes in the blood-brain barrier. Using an object recognition test and Y-maze, we found significant improvement in cognition in the treated group. Our findings support the potential use of a macrophage immunomodulator as a novel approach to reduce cerebrovascular amyloid, prevent microhemorrhage, and improve cognition.
KW - Cerebrovascular disease
KW - Cognitive impairment
KW - Intracerebral hemorrhage
KW - Macrophage
KW - MRI
KW - Therapy
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=82755194885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82755194885&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2011.01.006
DO - 10.1016/j.neurobiolaging.2011.01.006
M3 - Article
C2 - 21371785
AN - SCOPUS:82755194885
VL - 33
SP - 432.e1-432.e13
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 2
ER -