OO198 - LABEL-FREE VIBRATIONAL IMAGING OF DIFFERENT AΒ PLAQUE TYPES IN ALZHEIMER’S DISEASE REVEALS SEQUENTIAL EVENTS IN PLAQUE DEVELOPMENT (ID 1551)
Abstract
Aims
The neuropathology of Alzheimer’s disease (AD) is characterized by hyperphosphorylated tau neurofibrillary tangles and amyloid beta (Aβ) plaques. Aβ plaques are hypothesized to follow a development sequence starting with diffuse plaques, which evolve into more compact plaques and finally mature into the classic cored plaque type. A better molecular understanding of Aβ pathology is crucial, as the role of Aβ plaques in AD pathogenesis is under debate.
Methods
We studied the deposition and fibrillation of Aβ in different plaque types with label-free infrared imaging. Fourier-transform infrared (FTIR) imaging was performed on native snap-frozen brain tissue sections from AD cases and non-demented control cases. Subsequently, the scanned tissue was stained against Aβ and annotated for the different plaque types by an AD neuropathology expert. In total, 160 plaques (68 diffuse, 32 compact, and 60 classic cored plaques) were imaged with FTIR.
Results
In diffuse plaques, we detect evidence of short antiparallel β-sheets, suggesting the presence of Aβ oligomers. Aβ fibrillation significantly increases alongside the proposed plaque development sequence. In classic cored plaques, we spatially resolve cores containing predominantly large parallel β-sheets, indicating Aβ fibrils.
Conclusions
Combining label-free infrared imaging and immunohistochemistry on brain tissue samples of AD and non-demented cases provides novel insight into the spatial distribution of the Aβ conformations in different plaque types. This way, we reconstruct the development process of Aβ plaques in human brain tissue, provide insight into Aβ fibrillation in the brain, and provide new implications for therapeutic approaches.
