Antiphospholipid syndrome induction exacerbates a transgenic Alzheimer disease model on a female background.
The antiphospholipid syndrome (APS) is characterized by antiphospholipid antibodies (aPL) and vascular brain disease which is often associated with dementia. We examined the neurodegenerative pathological processes underlying APS by inducing APS in a transgenic animal model of Alzheimer's disease. Female C57B6/SJL mice carrying the APP(695)SWE mutation (Tg2576) and wild-type (wt) controls were immunized with β₂-glycoprotein-I (APS mice) or adjuvant alone (controls) at 4 months of age. At the age of 8 months the APP-APS mice developed high levels of aPL associated with motor hypoactivity in a staircase test (p<0.03 by t-test) and impaired performance in the cognitive T-maze (p<0.02 for main effect of treatment by repeated measures ANOVA) relative to APP-CFA mice and controls. wt-APS and wt-control did not differ significantly in their behavior or cognition. Histological studies revealed mature plaques only in the APP-APS group which also had higher amyloid load and number of activated microglia compared to all other groups. The results indicate a significant interaction between APP genotype and the induction of APS on a female background. The mechanisms involved may also be important in human APS-AD co-morbidity.
Katzav
Aviva
A
Department of Neurology and Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, 52621, Israel. katzava@post.tau.ac.il
Faust-Socher
Achinoam
A
Kvapil
Filip
F
Michaelson
Daniel M
DM
Blank
Miri
M
Pick
Chaim G
CG
Shoenfeld
Yehuda
Y
Korczyn
Amos D
AD
Chapman
Joab
J
D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D016736:Antiphospholipid Syndrome / Q000139:chemically induced / Q000150:complications*; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant / Q000009:adverse effects; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011597:Psychomotor Performance; D013550:Swimming; D053482:beta 2-Glycoprotein I / Q000009:adverse effects / Q000276:immunology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001323:Autoantibodies; D053482:beta 2-Glycoprotein I; D005620:Freund's Adjuvant