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In vivo detection of tau fibrils and amyloid beta aggregates with luminescent conjugated oligothiophenes and multiphoton microscopy
Massachusetts Gen Hosp, MA 02129 USA; Harvard Med Sch, MA 02129 USA.
Massachusetts Gen Hosp, MA 02129 USA; Harvard Med Sch, MA 02129 USA.
Massachusetts Gen Hosp, MA 02129 USA; Harvard Med Sch, MA 02129 USA.
Massachusetts Gen Hosp, MA 02129 USA; Harvard Med Sch, MA 02129 USA.
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2019 (English)In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 7, no 1, article id 171Article in journal (Refereed) Published
Abstract [en]

The detection of amyloid beta deposits and neurofibrillary tangles, both hallmarks of Alzheimers disease (AD), is key to understanding the mechanisms underlying these pathologies. Luminescent conjugated oligothiophenes (LCOs) enable fluorescence imaging of these protein aggregates. Using LCOs and multiphoton microscopy, individual tangles and amyloid beta deposits were labeled in vivo and imaged longitudinally in a mouse model of tauopathy and cerebral amyloidosis, respectively. Importantly, LCO HS-84, whose emission falls in the green region of the spectrum, allowed for the first time longitudinal imaging of tangle dynamics following a single intravenous injection. In addition, LCO HS-169, whose emission falls in the red region of the spectrum, successfully labeled amyloid beta deposits, allowing multiplexing with other reporters whose emission falls in the green region of the spectrum. In conclusion, this method can provide a new approach for longitudinal in vivo imaging using multiphoton microscopy of AD pathologies as well as other neurodegenerative diseases associated with protein aggregation in mouse models.

Place, publisher, year, edition, pages
BMC , 2019. Vol. 7, no 1, article id 171
Keywords [en]
Alzheimers disease; Amyloid beta plaques; Cerebral amyloid angiopathy; Luminescence; Multiphoton microscopy; Neurofibrillary tangles; Oligothiophenes; Tau
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-162529DOI: 10.1186/s40478-019-0832-1ISI: 000496490500002PubMedID: 31703739OAI: oai:DiVA.org:liu-162529DiVA, id: diva2:1376503
Note

Funding Agencies|NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AG044263, AG060974, 1U01NS110437-01]; Swedish Research CouncilSwedish Research Council [2016-00748]; BrightFocus FoundationBrightFocus Foundation [A2019488F]; Alzheimers AssociationAlzheimers Association [2018-AARF-591935]

Available from: 2019-12-09 Created: 2019-12-09 Last updated: 2020-01-22

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