In vivo detection of tau fibrils and amyloid beta aggregates with luminescent conjugated oligothiophenes and multiphoton microscopy

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.
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]