scholarly journals Age-Dependent Neurovascular Dysfunction and Damage in a Mouse Model of Cerebral Amyloid Angiopathy

Stroke ◽  
2014 ◽  
Vol 45 (6) ◽  
pp. 1815-1821 ◽  
Author(s):  
Laibaik Park ◽  
Kenzo Koizumi ◽  
Sleiman El Jamal ◽  
Ping Zhou ◽  
Mary Lou Previti ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Age Dependent ◽  
Cerebral Amyloid ◽  
Neurovascular Dysfunction

P3-464: CARBONIC ANHYDRASE INHIBITORS AMELIORATE NEUROVASCULAR DYSFUNCTION IN A MOUSE MODEL OF CEREBRAL AMYLOID ANGIOPATHY

2006 ◽  
Vol 14 (7S_Part_24) ◽  
pp. P1296-P1296 ◽  
Author(s):  
Federica Angiulli ◽  
Maria E. Solesio ◽  
Ludovic Debure ◽  
Jaime Ramos Cejudo ◽  
Thomas Wisniewski ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Mouse Model ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Carbonic Anhydrase Inhibitors ◽  
Cerebral Amyloid ◽  
Neurovascular Dysfunction

scholarly journals Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy

Brain ◽  
2007 ◽  
Vol 130 (9) ◽  
pp. 2310-2319 ◽  
Author(s):  
H. K. Shin ◽  
P. B. Jones ◽  
M. Garcia-Alloza ◽  
L. Borrelli ◽  
S. M. Greenberg ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Cerebral Amyloid Angiopathy ◽  
Transgenic Mouse Model ◽  
Amyloid Angiopathy ◽  
Cerebrovascular Dysfunction ◽  
Age Dependent ◽  
Cerebral Amyloid

Abstract WP397: Longitudinal Sex Differences in Cerebral Amyloid Angiopathy

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Michael Maniskas ◽  
Jacob Hudobenko ◽  
Akhiko Urayama ◽  
Louise McCullough ◽  
Bharti Manwani
Keyword(s):  
Mouse Model ◽  
Cerebral Amyloid Angiopathy ◽  
Cognitive Deficits ◽  
Elderly Women ◽  
Amyloid Plaque ◽  
Amyloid Angiopathy ◽  
Female Mice ◽  
Plaque Deposition ◽  
Significant Difference ◽  
Cerebral Amyloid

Background: Cerebral amyloid angiopathy (CAA) is the most common cause of lobar intracerebral hemorrhage in the aging population. It is mostly a consequence of amyloid beta40 (Aβ40) deposition within the cerebral blood vessels. A recent study has shown that this amyloid plaque deposition is more prevalent in the brain of elderly women compared to men. The increase in amyloid plaque deposition is linked to increased cerebral microbleeds (CMBs) and reduced cognition. The major objective of this study to discern if a sexual dichotomy existed in CMBs and cognition using mouse model of CAA. Methods: We used the Tg-SwDI mouse (“CAA mouse”, harboring Swedish, Dutch, and Iowa mutations of human amyloid precursor protein) model that develops Aβ deposits and cognitive deficits at 3-4 months. Cognitive deficits were analyzed using Fear Conditioning (FC) in pre-symptomatic (3 month) and (12 month) old male and female mice. Briefly, mice were acclimated to the FC chamber for a 2 minute training trial to record baseline. After 1 hour rest, mice were placed back in the chamber for 2 minutes, where they received a 2 millisecond shock (1,000 u/amp). Day 2, activity was recorded for 3 minutes and this measure was compared to baseline to determine Mean Inactive State (MIS-seconds). Mice were euthanized following FC, and brains scanned ex vivo using a MRI T2 Star sequence to assess for CMBs. Results: FC showed a significant difference in MIS (p<0.05) between male (3 and 12 months old) and female (3 months only) mice, n=6/group, suggesting that aged females had significantly lower MIS (Figure 1). MRI showed that aged female mice had more CMBs compared to aged male mice (females, 15.3±7 vs. males 0.25 ±0.2, n= 3/group, p=0.05. Conclusion: In a mouse model of CAA, our results demonstrate that aged females have increased CMBs as compared to males, which may be contributing to decreased cognition as seen on FC. Ongoing studies are designed to further understand the etiology of this sex difference.

scholarly journals Therapeutic Modulation of Cerebral Microhemorrhage in a Mouse Model of Cerebral Amyloid Angiopathy

Stroke ◽  
2011 ◽  
Vol 42 (11) ◽  
pp. 3300-3303 ◽  
Author(s):  
Mark Fisher ◽  
Vitaly Vasilevko ◽  
Giselle F. Passos ◽  
Christopher Ventura ◽  
Daniel Quiring ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Cerebral Microhemorrhage ◽  
Cerebral Amyloid

scholarly journals Endothelial expression of human APP leads to cerebral amyloid angiopathy in mice

2020 ◽  
Author(s):  
Yuriko Tachida ◽  
Saori Miura ◽  
Rie Imamaki ◽  
Naomi Ogasawara ◽  
Hiroyuki Takuwa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Β ◽  
Blood Levels ◽  
Amyloid Angiopathy ◽  
Disease Mechanisms ◽  
Age Dependent ◽  
Cerebral Amyloid ◽  
The Brain

AbstractThe deposition of amyloid β (Aβ) in blood vessels of the brain, known as cerebral amyloid angiopathy (CAA), is observed in more than 90% of Alzheimer’s disease (AD) patients. The presence of such CAA pathology is not as evident, however, in most mouse models of AD, thereby making it difficult to examine the contribution of CAA to the pathogenesis of AD. Since blood levels of soluble amyloid precursor protein (sAPP) in rodents are less than 1% of those in humans, we hypothesized that endothelial APP expression would be markedly lower in rodents, thus providing a reason for the poorly expressed CAA pathology. Here we generated mice that specifically express human APP770 in endothelial cells. These mice exhibited an age-dependent robust deposition of Aβ in brain blood vessels but not in the parenchyma. Crossing these animals with APP knock-in mice led to an expanded CAA pathology as evidenced by increased amounts of amyloid accumulated in the cortical blood vessels. These results show that both neuronal and endothelial APP contribute cooperatively to vascular Aβ deposition, and suggest that this mouse model will be useful for studying disease mechanisms underlying CAA and for developing novel AD therapeutics.

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