| 60688 |
Creator |
d64a4c8b9d6fb32d441f1cd9c453d93b |
| 60688 |
Creator |
6bc25fd5e28aacb583a3a221cae96030 |
| 60688 |
Creator |
ext-29d78d170fa0d369678be999019ef36d |
| 60688 |
Date |
2019 |
| 60688 |
Date |
2019-12 |
| 60688 |
Is Part Of |
repository |
| 60688 |
Is Part Of |
p13652990 |
| 60688 |
abstract |
<b>Aims</b>
<br></br>Apolipoprotein A‐I (apoA‐I), the principal apolipoprotein associated with
high density lipoproteins (HDL) in the periphery, is also found at high concentrations
in the cerebrospinal fluid. Previous studies have reported either no impact or vascular‐specific
effects of apoA‐I knockout on β‐amyloid (Aβ) pathology. However, the putative mechanism(s)
by which apoA‐I may influence Aβ deposition is unknown.
<br></br><br></br><b>Methods</b>
<br></br>We evaluated the effect of apoA‐I deletion on Aβ pathology, Aβ production
and clearance from the brain in the Tg2576 mouse model of AD.
<br></br><br></br><b>Results</b>
<br></br>Contrary to previous reports, deletion of the <i>APOA1</i> gene significantly
reduced concentrations of insoluble Aβ40 and Aβ42 and reduced plaque load in both
the parenchyma and blood vessels of apoA‐I knockout x Tg2576 mice compared to Tg2576
animals. This was not due to decreased Aβ production or alterations in Aβ species.
Levels of soluble clusterin/apoJ were significantly higher in neurons of apoA‐I KO
mice compared to both wildtype and apoA‐I KO x Tg2576 mice. In addition, clearance
of Aβ along intramural periarterial drainage pathways was significantly higher in
apoA‐I KO mice compared to wildtype animals.
<br></br><br></br><b>Conclusion</b>
<br></br>These data suggest that deletion of apoA‐I is associated increased clearance
of Aβ and reduced parenchymal and vascular Aβ pathology in the Tg2576 model. These
results suggest that peripheral dyslipidaemia can modulate the expression of apolipoproteins
in the brain and may influence Aβ clearance and aggregation in AD. |
| 60688 |
authorList |
authors |
| 60688 |
issue |
7 |
| 60688 |
status |
published |
| 60688 |
status |
peerReviewed |
| 60688 |
volume |
45 |
| 60688 |
type |
AcademicArticle |
| 60688 |
type |
Article |
| 60688 |
label |
Contu, Laura ; Carare, Roxana O. and Hawkes, Cheryl A. (2019). Knockout of apolipoprotein
A‐I decreases parenchymal and vascular β‐amyloid pathology in the Tg2576 mouse model
of Alzheimer's disease. Neuropathology and Applied Neurobiology, 45(7) pp. 698–714. |
| 60688 |
label |
Contu, Laura ; Carare, Roxana O. and Hawkes, Cheryl A. (2019). Knockout of apolipoprotein
A‐I decreases parenchymal and vascular β‐amyloid pathology in the Tg2576 mouse model
of Alzheimer's disease. Neuropathology and Applied Neurobiology (Early Access).
|
| 60688 |
Publisher |
ext-e7795bc59c66fd1972aa29b4459edb20 |
| 60688 |
Title |
Knockout of apolipoprotein A‐I decreases parenchymal and vascular β‐amyloid pathology
in the Tg2576 mouse model of Alzheimer's disease |
| 60688 |
in dataset |
oro |