BEGIN:VCALENDAR PRODID:-//eluceo/ical//2.0/EN VERSION:2.0 CALSCALE:GREGORIAN BEGIN:VEVENT UID:9e34032da5497ceb6e1ad01d57170320 DTSTAMP:20261017T143641Z SUMMARY:Nils Lindblom - Institutionen för experimentell medicinsk vetenska p DESCRIPTION:Kontakt: nils.lindblom@med.lu.se\n\nTitle: Anti-amyloid immunot herapies for Alzheimer's diseaseMain supervisor: Gunnar GourasReviewers: K atrin Mani\, Lars Tjernberg\, \;Yiyi YangAbstractBackgroundAlzheimer ’s disease is the leading cause of dementia and an increasing public hea lth concern globally as our lifespan increases. The first disease modifyin g treatments for the disease\, antibodies targeting Aβ\, demonstrated suc cessful clinical trials 3 years ago and are now in clinical use around the world. Remarkably\, the mechanism(s) for the beneficial effect of immunot herapy against amyloid-beta remain unclear.Research questionsAre soluble p rotofibrils a better correlate to the drop in CSF \;Aβ42/40 ratio and increase in the neurodegeneration markers nfl\, t-tau \;in AD than pl aques?What are the precise anatomical and cellular localization of \;A β antibodies in the brain after \;Aβ immunotherapy?How does lecanema b affect the different cell types of the brain?How are CSF and plasma biom arkers changed over time with \;Aβ antibody treatment?Preliminary res ultsIn the first paper we demonstrated that the correlation between amyloi d plaques and CSF markers of pathology/neurodegeneration are mediated by A β protofibrils and that the CSF Aβ42/40 ratio\, corresponding to protofi brils\, provides different information compared to Aβ PET\, corresponding to Aβ plaques. In the second paper we show that Aβ antibodies widely di stribute in the brain and localize to several cell types\, including AD vu lnerable neurons\, astrocytes\, microglia and perivascular macrophages.In the third paper/manuscript that is ongoing we show that lecanemab reduces brain amyloid pathology and tau phosphorylation. Importantly\, lecanemab a ffects all the major cell types in the brain\; neurons\, microglia\, oligo dendrocytes\, OPCs and astrocytes. In neurons\, lecanemab reduces choleste rol synthesis and Bace1 protein level while increasing synaptic translatio n. \;In the final paper/manuscript we demonstrate that Aβ antibodies can be taken up by neurons\, where they help clear intraneuronal amyloid a ggregates. \;SignificanceAβ immunotherapy is the first and only disea se modifying treatment for AD. An increased understanding of the biologica l effect of these treatments can help aid the development of new and impro ved immunotherapies for the AD. \;Published studies \;1. \;htt ps://www.nature.com/articles/s43587-025-00810-82. \;https://alz-journa ls.onlinelibrary.wiley.com/doi/10.1002/alz.71121\n\nMer information om hä ndelsen: https://www.intramed.lu.se/evenemang/nils-lindblom-institutionen- experimentell-medicinsk-vetenskap DTSTART;TZID=GMT:20260824T110000 DTEND;TZID=GMT:20260824T110000 LOCATION:BMC:I1345 Sölvegatan 19\, 223 62 Lund END:VEVENT END:VCALENDAR