title: Postmortem 3-D brain hemisphere cortical tau and amyloid-β pathology mapping and quantification as a validation method of neuropathology imaging.
abstract: This work is aimed at correlating pre-mortem [18F]FDDNP positron emission tomography (PET) scan results in a patient with dementia with Lewy bodies (DLB), with cortical neuropathology distribution determined postmortem in three physical dimensions in whole brain coronal sections. Analysis of total amyloid-β (Aβ) distribution in frontal cortex and posterior cingulate gyrus confirmed its statistically significant correlation with cortical [18F]FDDNP PET binding values (distribution volume ratios, DVR) (p < 0.001, R = 0.97, R2 = 0.94). Neurofibrillary tangle (NFT) distribution correlated significantly with cortical [18F]FDDNP PET DVR in the temporal lobe (p < 0.001, R = 0.87, R2 = 0.76). Linear combination of Aβ and NFT densities was highly predictive of [18F]FDDNP PET DVR through all analyzed regions of interest (p < 0.0001, R = 0.92, R2 = 0.85), and both densities contributed significantly to the model. Lewy bodies were present at a much lower level than either Aβ or NFTs and did not significantly contribute to the in vivo signal. [18F]FDG PET scan results in this patient were consistent with the distinctive DLB pattern of hypometabolism. This work offers a mapping brain model applicable to all imaging probes for verification of imaging results with Aβ and/or tau neuropathology brain distribution using immunohistochemistry, fluorescence microscopy, and autoradiography.
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6948, USA.
authors.forename: Lojze M
authors.initials: LM
authors.lastname: Smid
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Mara
authors.initials: M
authors.lastname: Bresjanac
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toyokuni
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: Koon-Pong
authors.initials: KP
authors.lastname: Wong
authors.forename: Sung-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Daniel H S
authors.initials: DH
authors.lastname: Silverman
authors.forename: Karen
authors.initials: K
authors.lastname: Miller
authors.forename: Gary W
authors.initials: GW
authors.lastname: Small
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D021621:Imaging, Three-Dimensional; D020961:Lewy Body Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D016874:Neurofibrillary Tangles; D009570:Nitriles; D049268:Positron-Emission Tomography; D011180:Postmortem Changes; D011569:Psychiatric Status Rating Scales; D015203:Reproducibility of Results; D015898:Tomography Scanners, X-Ray Computed; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D016229:Amyloid beta-Peptides; D009570:Nitriles; D016875:tau Proteins