The Progress of Label-Free Optical Imaging in Alzheimer’s Disease Screening and Diagnosis

Abstract

As the major neurodegenerative disease of dementia, Alzheimer’s disease (AD) has caused an enormous social and economic burden on society. Currently, AD has neither clear pathogenesis nor effective treatments. Positron emission tomography (PET) and magnetic resonance imaging (MRI) have been verified as potential tools for diagnosing and monitoring Alzheimer’s disease. However, the high costs, low spatial resolution, and long acquisition time limit their broad clinical utilization. The gold standard of AD diagnosis routinely used in research is imaging AD biomarkers with dyes or other reagents, which are unsuitable for in vivo studies owing to their potential toxicity and prolonged and costly process of the U.S. Food and Drug Administration (FDA) approval for human use. Furthermore, these exogenous reagents might bring unwarranted interference to mechanistic studies, causing unreliable results. Several label-free optical imaging techniques, such as infrared spectroscopic imaging (IRSI), Raman spectroscopic imaging (RSI), optical coherence tomography (OCT), autofluorescence imaging (AFI), optical harmonic generation imaging (OHGI), etc., have been developed to circumvent this issue and made it possible to offer an accurate and detailed analysis of AD biomarkers. In this review, we present the emerging label-free optical imaging techniques and their applications in AD, along with their potential and challenges in AD diagnosis.

FTIR Spectroscopy and Blood-Derived Extracellular Vesicles Duo in Alzheimer’s Disease

“…In agreement with our FTIR spectra observations for bdEVs, altered patterns in the Amide I region were also reported for human blood, blood peripheral mononuclear leukocytes or CSF, particularly an increase in peaks intensity assigned to β-sheets in AD cases [ 18, 23–25, 54 ]. The EVs’ role in AD is still not fully understood but it is certain that EVs transport several AD pathogenic proteins such as Aβ and tau species, in oligomer or aggregated forms [ 55–58 ], composed of stable β-sheets [ 59 ]. Data here presented support that EVs can be involved in protein aggregated forms spreading.…”

Neuroimaging modalities in the detection of Alzheimer's disease-associated biomarkers

“…In addition, nuclear imaging modalities have some disadvantages, such as high cost, poor resolution, long testing times, and unavoidable exposure to radioactivity (Xu et al ., 2016 ). Optical imaging modalities, particularly NIRF imaging, may provide a non-invasive in vivo method to visualize the real-time status of the AD brains more accurately at the biomolecular level (Liu et al ., 2021b ; López-Cuenca et al ., 2021 ). Importantly, small molecule NIR probes are used to detect Tau protein, β-amyloid, and other biomarkers (Rai et al ., 2022 ).…”

“…Importantly, small molecule NIR probes are used to detect Tau protein, β-amyloid, and other biomarkers (Rai et al ., 2022 ). Optical imaging applications can simultaneously record and analyse both the spatial and functional dynamics of pathological injuries (Liu et al ., 2021b ).…”

Recent Advances in Fluorescent Theranostics for Alzheimer’s Disease: A Comprehensive Survey on Design, Synthesis, and Properties

“…17 In contrast to these classic imaging techniques, optical imaging is gradually becoming an attractive modality in research and clinical practice, holding the advantages of ease of operation, fast response time, high sensitivity, no exposure to radiation, and noninvasive target imaging for living animals. 20 In fact, the postmortem AD diagnosis widely uses Congo red (CR) and thioflavin T (ThT) (Figure 3) as fluorescent dyes for the histological staining of amyloid fibrils. 21−23 Structurally, ThT is a cationic benzothiazole fluorescent dye having a hydrophobic edge with a dimethylaminophenyl group, which is linked to a benzothiazolium containing the polar N and S atoms.…”