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bioRxiv · 10.1101/2020.03.08.982363

Conjugates of neuroprotective chaperone L-PGDS provide MRI contrast for detection of amyloid β-rich regions in live Alzheimer's Disease mouse model brain

Sharma, B.·Grandjean, J.·Phillips, M.·Kumar, A.·Mandino, F.·Yeow, L.-Y.·Nandwana, V.·Dravid, V. P.·Bengang, X.·Lim, S.·Pervushin, K.
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Abstract

Endogenous brain proteins can recognize the toxic oligomers of amyloid-{beta} (A{beta}) peptides implicated in Alzheimers disease (AD) and interact with them to prevent their aggregation. Lipocalin-type Prostaglandin D Synthase (L-PGDS) is a major A{beta}-chaperone protein in the human cerebrospinal fluid. Here we demonstrate that L-PGDS detects amyloids in diseased mouse brain. Conjugation of L-PGDS with magnetic nanoparticles enhanced the contrast for magnetic resonance imaging. We conjugated the L-PGDS protein with ferritin nanocages to detect amyloids in the AD mouse model brain. We show here that the conjugates administered through intraventricular injections co-localize with amyloids in the mouse brain. These conjugates can target the brain regions through non-invasive intranasal administration, as shown in healthy mice. These conjugates can inhibit the aggregation of amyloids in vitro and show potential neuroprotective function by breaking down the mature amyloid fibrils.

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Sharma, B., Grandjean, J., Phillips, M., Kumar, A., Mandino, F., Yeow, L.-Y., Nandwana, V., Dravid, V. P., Bengang, X., Lim, S., Pervushin, K.. 2020-03-09. Conjugates of neuroprotective chaperone L-PGDS provide MRI contrast for detection of amyloid β-rich regions in live Alzheimer's Disease mouse model brain. https://doi.org/10.1101/2020.03.08.982363

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