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P2‐423: vMRI and whole‐brain volume in patients with mild‐to‐moderate Alzheimer's disease
Author(s) -
Budd David,
Nalysnyk Luba,
Fahrbach Kyle,
Bhagwagar Zubin,
Berman Robert,
Burns Leah,
l'Italien Gilbert
Publication year - 2012
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.2012.05.2048
Subject(s) - atrophy , medicine , brain size , disease , alzheimer's disease neuroimaging initiative , meta analysis , magnetic resonance imaging , alzheimer's disease , radiology
with Alzheimer’s Disease (AD) is being tested in different clinical trials. Flebogamma DIF (Grifols’ IVIG) modifies plasma beta-amyloid (Aß) levels similarly to other IVIGs and to Albutein combined with plasmapheresis/plasma exchange. This would support the feasibility of a combined treatment of IVIG with albumin in plasmapheresis looking for a synergistic effect. AD is characterized by neurodegeneration and vascular damage associated with Aß deposits in brain parenchyma and cerebral vessels. IVIG efficacy in AD may depend on immune system modulation and/or direct Aß targeting. In this study we investigated the effect of Flebogamma DIF on the toxicity caused by Aß aggregates in primary cultures of cortical neurons and endothelial cells.Methods: Human synthetic Aß 1-42 peptide was dissolved in dimethyl sulfoxide (500 mM) and diluted in culture medium, with or without IVIG, to a final 1mM Aß concentration. Solutions were stirred continuously (3 hours, 37 C) to obtain oligomers, or stirred (48 hours plus 5 days incubation, 37 C) to obtain mature amyloid fibrils, which were used immediately after preparation. Primary cultures of murine cortical neurons and porcine aortic endothelium were incubated during 24 h with: i) Aß pre-aggregated without IVIG and subsequent IVIG addition (0.07-7mg/ml); and ii) Aß pre-aggregated with IVIG (0.07-7mg/ml). Cell survival (CS) was quantified using the MTT assay. Results: Flebogamma DIF showed a protective effect against Aß toxicity in mature cortical neurons (CS: 100.8%-103.7% versus 78.9%), which increased when IVIG was added during oligomer formation (CS: 110.5%-132.5%). However, Flebogamma DIF did not appear to protect neurons against the toxicity of Aß mature fibrils. In endothelial cells, the protective effect was significant only when Flebogamma DIF was present during oligomer or fibril aggregation (CS: 96.9%-100.1% and 91.9%-94.4%, versus 78.6% and 87.2% respectively). Conclusions: Our data suggest that Flebogamma DIF possesses a neuroprotective effect, which may be linked to its ability to inhibit both the formation of highly neurotoxic oligomers and the toxic properties of already formed oligomers.