Aβ plaque-selective NIR fluorescence probe to differentiate Alzheimer's disease from tauopathies

• Selective detection and staining of toxic amyloid plaques, a potential biomarker present in the Alzheimer's disease (AD) brain is crucial for both clinical diagnosis and monitoring AD disease progression. Herein, we report a coumarin-quinoline (CQ) conjugate-based turn-on near-infrared (NIR) fluorescence probe for specific detection of β-amyloid (Aβ) aggregates. CQ probe is highly sensitive and exhibits ~100-fold fluorescence enhancement in vitro upon binding Aβ aggregates with enhanced quantum yield. Furthermore, the probe has ~10-fold higher binding affinity towards Aβ aggregates (86 nM) compared to commonly used Thioflavin T. Most importantly, CQ probe displays unambiguous selectivity towards Aβ aggregates compared to other toxic protein aggregates such as tau, α-synuclein (α-Syn) and islet amyloid polypeptide (IAPP). In addition, CQ is nontoxic to neuronal cells and shows significant blood brain barrier permeability. Remarkably, CQ stains Aβ plaques in human brain tissue over co-existing tau aggregates and neurofibrillary tangles (NFTs), which are associated in AD and tauopathies. This is a highly desirable attribute to distinguish AD from tau pathology and mixed dementia.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)

Nyckelord

Alzheimer's disease

Mixed dementia

Neurofibrillary tangles (NFTs)

NIR fluorescence probes

Selective detection of Aβ42 plaques

Tauopathies

Aggregates

Binding energy

Bins

Brain

Diagnosis

Fluorescence

Glycoproteins

Infrared devices

Probes

Neurofibrillary tangles

NIR fluorescences

Selective detection

Neurodegenerative diseases

alpha synuclein

amylin

amyloid beta protein

coumarin

quinoline

tau protein

thioflavine

Alzheimer disease

amyloid plaque

analytic method

Article

binding affinity

binding site

blood brain barrier

brain tissue

calculation

controlled study

fluorescence analysis

fluorescence resonance energy transfer

human

human tissue

in vitro study

molecular docking

molecular weight

near infrared fluorescence probe

neurofibrillary tangle

physical chemistry

protein aggregation

protein folding

quantum yield

tauopathy

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)