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P2‐469: Toward therapeutic system for Alzheimer's Disease by removal of blood Aβ: Hemodialysis improved the impaired cognitive states of renal failure patients
Author(s) -
Kitaguchi Nobuya,
Kawaguchi Kazunori,
Kato Masao,
Nakai Shigeru,
Murakami Kazutaka,
Ito Shinji,
Hori Hideo,
Ohashi Atsushi,
Shimano Yasunobu,
Suzuki Nobuo,
Sugiyama Satoshi,
Hiki Yoshiyuki,
Mutoh Tatsuro,
Yuzawa Yukio
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1341
Subject(s) - hemodialysis , medicine , creatinine , chronic renal failure , disease , urology , gastroenterology , endocrinology
Background: Active anti-amyloid immunotherapy is a strategy developed against Alzheimer’s disease.ApproacheswithAs1-42 orK6As1-30 immunogens in an adjuvant decrease amyloid-s burden and prevent cognitive decline in transgenic mice (Asuni et al, 2006). However, clinical trials of As1-42 immunotherapy have induced side effects like encephalitis and possibly microhemorrhages (Orgogozo et al, 2003; Ferrer et al, 2004). Mouse lemurs can develop As plaques with age (Mestre-Franc es et al, 2000). Such a primate model may bemore predictive than rodents of human side effects.We studied, by magnetic resonance imaging (MRI), immunotherapies in these primates. Methods: A first cohort was used to compare K6As1-30 (n 1⁄4 4; 5.8 6 0.2years) and As1-42 (n1⁄4 4; 5.96 0.2years) immunogens in alum adjuvant. A second cohort was used to evaluateK6As1-30 (n1⁄4 6; 4.66 0.2years) compared to adjuvant alone (n 1⁄4 6; 4.7 6 0.3years). All the animals were followed-up by MRI (7T PharmaScan-Bruker) to evaluate neuroinflammation, microhemorrhages and other forms of iron deposition, with T2-weighted and T2*-weighted sequences (resolution 1⁄4 (234x234x234)Âmm3). The hypointense regions from T2*-weighted images were quantified and evaluate by histology. A complementary study of age effect was performed with twenty other naive animals (1.5 to 4.9years). Results: TheT2-weighted images did not show any neuroinflammation during immunization, irrespective of the immunogen. Microhemorrhages were detected in the cerebral parenchyma at the histological analysis of the first cohort. The animals treated with K6As1-30 presented less microhemorrhages compared to those treated with As1-42 vaccine (Mann-Whitney, p< 0.05). These small microhemorrhages were not detected on the T2*-weighted images. However hypointense signal was detected on MRI and corresponded to iron deposits in the choroid plexus. Its volume increased with natural aging (r1⁄4 0.60; p< 0.001) and with As1-42 compared toK6As1-30 treatment (ANOVA, p< 0.05). No difference was detected between K6As1-30 and adjuvant alone. Conclusions: The immunotherapies studied in the mouse lemur primate did not lead to any MRI sign of neuroinflammation. The K6As1-30 strategy appears to be safer than the As1-42 strategy as it provokes less microhemorrhages in the cerebral parenchyma and less iron deposits in the choroid plexus.