Post-mortem analyses of PiB and flutemetamol in diffuse and cored amyloid- β plaques in Alzheimer’s disease

AbstractSpecificity and sensitivity of positron emission tomography (PET) radiopharmaceuticals targeting fibrillar amyloid- β (Aβ) deposits is high for detection of neuritic Aβ plaques, a mature form of Aβ deposits which often have dense Aβ core (i.e., cored plaques). However, imaging-to-autopsy validation studies of amyloid PET radioligands have identified several false positive cases all of which had mainly diffus e Aβ plaques (i.e., plaques without neuritic pathology or dense amyloid core), and high amyloid PET signal was reported in the striatum where diffuse plaques predominate in Alzheimer’s disease (AD). Relative contributions of different plaque types to amyloid PET signal is unclear, particularly in neocortical areas where they are intermixed in AD. In vitro binding assay and autoradiography were performed using [3H]flutemetamol and [3H]Pittsburgh Compound-B (PiB) in frozen brain homogenates from 30 autopsy cases including sporadic AD and non-AD controls with a range of brain A β burden and plaque density. Fixed tissue sections of frontal cortex and caudate from 10 of the AD cases were processed for microscopy using fluorescent derivatives of flutemetamol (cyano-flutemetamol) and PiB (cyano-PiB) and compared to Aβ immunohistochemistry and pan-amyloid (X-34) histology. Us ing epifluorescence microscopy, percent area coverage and fluorescence output values of cyano-PiB- and cyano-flutemetamol-labeled plaques in two-dimensional microscopic fields were then cal...
Source: Acta Neuropathologica - Category: Neurology Source Type: research