Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease, and β-amyloid (Aβ) is believed to be a causative factor in AD pathology. The abnormal deposition of Aβ is believed to be responsible for progression of AD. In order to facilitate the imaging of Aβ in vivo, suitable probe molecules with a near-infrared emission wavelength that can penetrate the blood–brain barrier (BBB) were utilized. The commercial fluorescent probe thioflavin-T (ThT) is used to image Aβ; however, because of its short emission wavelength and poor BBB penetration, ThT can only be used in vitro. With this research, based on ThT, we design three fluorescent probes (SZIs) having a longer emission wavelength in order to image Aβ aggregates. SZIs with different numbers of double bonds respond to Aβ aggregates. The SZIs have a structure similar to ThT, and as such, the SZIs are also unable to penetrate the BBB. To deal with the problem, we develop nanocomposites (MSN-Lf@SZIs) to deliver SZIs into the brain of AD mouse and image Aβ successfully. These new nanocomposites are able to deliver the dyes into the brain and facilitate Aβ imaging in vivo.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disease, and β-amyloid (Aβ) is believed to be a causative factor in AD pathology
Alzheimer’s disease (AD) is a neurodegenerative disease, whose major pathological feature is the progressive loss of neuronal functions.[1] β-amyloid (Aβ) is a proteolytic product of amyloid precursor protein (APP), which is a causative factor during AD pathology.[2]
ThT has some advantages for the detection of Aβ1−42, it has several inherent disadvantages such as poor blood−brain barrier (BBB) penetration and short emission wavelength [λem = 490 nm in phosphate buffer saline (PBS)]
Summary
Alzheimer’s disease (AD) is a neurodegenerative disease, and β-amyloid (Aβ) is believed to be a causative factor in AD pathology. The new nanocomposites facilitate the transfer of the SZIs into the brain for imaging Aβ1−42 in vivo. In vitro and in vivo experiments confirm that the nanocomposites of the MSN-Lf and SZIs are capable of imaging Aβ1−42 in the brain of the living mice.
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