Postmortem 3-D Brain Hemisphere Cortical Tau and Amyloid-β Pathology Mapping and Quantification as a Validation Method of Neuropathology Imaging

Article type: Research Article

Authors: Smid, Lojze M.^{a; b} | Kepe, Vladimir^a | Vinters, Harry V.^a | Bresjanac, Mara^b | Toyokuni, Tatsushi^a | Satyamurthy, Nagichettiar^a | Wong, Koon-Pong^a | Huang, Sung-Cheng^a | Silverman, Daniel H.S.^a | Miller, Karen^a | Small, Gary W.^a | Barrio, Jorge R.^{a; *}

Affiliations: [a] David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [b] School of Medicine, University of Ljubljana, Ljubljana, Slovenia

Correspondence: [*] Correspondence to: Jorge R. Barrio, PhD, David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, CHS B2-086A, 694817, 10833 Le Conte Avenue, Los Angeles, CA 90095-6948, USA. Tel.: +1 310 825 4167; Fax: +1 310 825 4517; E-mail: [email protected].

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.

Keywords: Amyloid, brain pathology mapping, dementia with Lewy bodies, [¹⁸F]FDDNP, immunocytochemistry, tau

DOI: 10.3233/JAD-122434

Journal: Journal of Alzheimer's Disease, vol. 36, no. 2, pp. 261-274, 2013