Abstract
We developed multimodal multiphoton microspectroscopy using a small-diameter probe with gradient-index lenses and applied it to unstained Alzheimer's disease (AD) brain samples. Our system maintained the image quality and spatial resolution of images obtained using an objective lens of similar numerical aperture. Multicolor images of AD brain samples were obtained simultaneously by integrating two-photon excited fluorescence and second-harmonic generation on a coherent anti-Stokes Raman scattering (CARS) microendoscope platform. Measurements of two hippocampal regions, the cornus ammonis-1 and dentate gyrus, revealed more lipids, amyloid fibers, and collagen in the AD samples than in the normal samples. Normal and AD brains were clearly distinguished by a large spectral difference and quantitative analysis of the CH mode using CARS microendoscope spectroscopy. We expect this system to be an important diagnosis tool in AD research
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that gradually destroys brain cells, causing changes in memory, thinking, and other brain functions.[1]
We measured the spectral difference in the C─H vibration stretching mode in normal and AD samples using coherent anti-Stokes Raman scattering (CARS) spectroscopy
We focused on the hippocampal cornus ammonis-1 (CA-1) and dentate gyrus (DG) regions in our measurements because these two areas are damaged during AD and are well-known to be involved in learning and memory
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that gradually destroys brain cells, causing changes in memory, thinking, and other brain functions.[1] Amyloid beta (Aβ; plaques), the primary constituent of senile plaques, and tau tangles are hypothesized to play a primary role in the pathogenesis of AD, but it is still hard to identify the fundamental mechanisms.[2,3,4] Several recent research papers reported that γ-aminobutyric acid (GABA) is an another important pathological hallmark of the AD brain.[5,6]. According to a recent World Alzheimer’s report, the number of people globally suffering from AD in 2013 is estimated to be 35 million, and epidemiological studies predict that this number will grow at an alarming rate.[7] This number is estimated to approximately double every 20 years to 65 million by 2030 and 115 million by 2050. AD is a major global health issue; reliable diagnosis and early detection are important.[7]
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