There is currently
no definitive test for early detection of neurodegeneration
which is linked with protein aggregation. Finding methods capable
of detecting intermediate states of protein aggregates, named oligomers,
is critical for the early stage diagnosis of over 30 neurodegenerative
diseases including Alzheimer’s or Parkinson’s. Currently,
fluorescence-based imaging using Thioflavin T (ThT) dye is the gold
standard for detecting protein aggregation. It is used to detect aggregation
in vitro and in various tissues, including the cerebrospinal fluid
(CSF), whereby the disease-related protein recombinant is seeded with
the patient’s fluid. The major drawback of ThT is its lack
of sensitivity to oligomeric forms of protein aggregates. Here, we
overcome this limitation by transferring a ThT–oligomer mixture
into solid state thin films and detecting fluorescence of ThT amplified
in the process of stimulated emission. By monitoring the amplified
spontaneous emission (ASE) we achieved a remarkable recognition sensitivity
to prefibrillar oligomeric forms of insulin and lysozyme aggregates
in vitro, to Aβ42 oligomers in the human protein recombinants
seeded with CSF and to Aβ42 oligomers doped into brain tissue.
Seeding with Alzheimer patient’s CSF containing Aβ42
and Tau aggregates revealed that only Aβ42 oligomers allowed
generating ASE. Thus, we demonstrated that, in contrast to the current
state-of-the-art, ASE of ThT, a commonly used histological dye, can
be used to detect and differentiate amyloid oligomers and evaluate
the risk levels of neurodegenerative diseases to potential patients
before the clinical symptoms occur.