Premium
Label‐free X‐ray technique for distinguishing 5XFAD from wild‐type mice
Author(s) -
Dahal Eshan,
Crentsil Jasson,
Ghammraoui Bahaa,
Badano Aldo
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043608
Subject(s) - olfactory bulb , hippocampus , chemistry , in vivo , amyloid (mycology) , wild type , pathology , biophysics , nuclear medicine , biology , medicine , endocrinology , biochemistry , central nervous system , mutant , microbiology and biotechnology , gene
Background We recently proposed a label‐free method based on spectral small‐angle x‐ray scattering (sSAXS) technique that estimates brain amyloid load in vivo in small animals. Here we present the first results of amyloid load mapping for an Alzheimer’s disease mouse model without using contrast agents. Method A prototype sSAXS system was built to collect elastic x‐ray scattering data from an intact mouse head at angles less than 10° and energies between 30 and 45 keV. 5XFAD mice along with age‐matched wild‐type (WT) controls were used in the study. Fixed mice heads were scanned from eye to ear at three different heights in a sagittal plane with a scanning step size of 2 mm. Data were acquired at each position for 300, 600, and 1200 seconds with repositioning of the target. The relative amyloid load was estimated by taking area‐under‐the‐peak (AUP) in the scattering profile from momentum transfer (q) 3.6 to 8.4 nm ‐1 . AUP analysis covers the characteristic signal of amyloid plaques associated with its beta‐sheet structure. Result Out of 15 scanned locations in mice heads using 300 s exposure time, areas associated with the isocortex and the olfactory bulb showed significantly increased AUP values with respect to WT mice. Midbrain regions showed negligible differences in AUPs. These results were further reproduced using 600 and 1200 s exposure times. Compared to WT, 5XFAD mice exhibited significantly elevated levels of amyloid plaques in the isocortex near hippocampus (9.3 ± 3.7%) and the olfactory bulb (10.8 ± 0.82 %). Our method was sensitive enough to differentiate brain regions with and without plaques despite the strong background scattering signal from the skull and other brain tissues. Conclusion Our results showcase the capability of sSAXS based method to differentiate non‐diseased and diseased mice by estimating amyloid load in Alzheimer’s disease mouse model ex vivo or in vivo and without using any contrast agent. Intrinsic small‐angle x‐ray scattering signal from beta‐amyloid plaques in diseased mice with advanced Alzheimer's allows the differentiation of brain regions with a high amyloid load.