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- W2103179221 abstract "Immunotherapies that target the Aβ peptide in AD have consistently resulted in amyloid clearance and cognitive improvements in mouse studies, and this effect is likely mediated by antibodies. Despite the setbacks associated with the initial human clinical trials, promising preliminary findings have emerged. These include reduction in amyloid burden and cognitive stabilization. Refinement of this approach is currently underway. Another important target in AD is the neurofibrillary tangles which correlate well with the degree of dementia. Histological analysis in AD brains and mouse models indicate that Aβ and tau pathologies are likely synergistic. Hence, targeting both pathologies at the same time may be more effective. Also, Aβ immunotherapy does not reduce tau aggregates in AD or mouse models, showing the importance of developing a separate tangle–targeting therapy. Clearance of extracellular tangles may reduce associated pathology, and numerous reports of neuronal uptake of antibodies suggest that intracellular tangles and pre–tangles may also be affected. To examine the effect of tau–based active immunotherapy targeting pathological tau conformers in transgenic P301L mice that develop neurofibrillary tangles and associated sensorimotor abnormalities. Homozygous P301L mice received intraperitoneal injections of a phospho–tau peptide derivative in alum adjuvant (n=12) or adjuvant only (n=13), starting at 2 months. Tau–specific immunoglobulin titers were determined and at 5 months their brains were processed for tau biochemistry and histology. A separate group of vaccinated mice (n=12) and controls (n=12) received injections from 2 months and were tested on various sensorimotor tasks (rotarod, traverse beam, locomotor activity) at 5 months. These animals will be retested periodically and their brains subsequently analyzed. The vaccine elicited a robust tau–specific antibody response, associated with a reduction in aggregated tau (47%; p<0.04) in the brain but soluble tau levels were unaltered, compared to the control group. The immunized animals performed better than the controls on the rotarod (p<0.02) and the traverse beam (p<0.001), and attained greater speed (Vmax) in the locomotor task (p<0.01). Histological evaluation is underway. Active immunization with a phospho–tau derivative peptide reduces brain levels of aggregated tau and slows the progression of tangle–related behavioral phenotype." @default.
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- W2103179221 date "2006-07-01" @default.
- W2103179221 modified "2023-09-27" @default.
- W2103179221 title "O2-05-04: Tau-based immunotherapy for dementia" @default.
- W2103179221 doi "https://doi.org/10.1016/j.jalz.2006.05.141" @default.
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