IC‐P‐063: A TOPOGRAPHIC IMAGING BIOMARKER OF TDP43 PATHOLOGY IN AMNESTIC DEMENTIA BASED ON AUTOPSY‐DERIVED FDG‐PET PATTERNS

• DOI: 10.1016/j.jalz.2019.06.4906
• Publication Date: 2019-10-18T11:59:48Z
• Authors: Michel J. Grothe; Catharina Lange; Kwangsik Nho; Andrew J. Saykin; Irina Jelistratova; Peter T. Nelson; Ralph Buchert; Stefan J. Teipel
• Keywords: Tau Pathology

Limbic TDP-43 pathology is a frequent neuropathologic finding in advanced age that associates with hippocampal sclerosis (HS) and can result amnestic deficits mimicking Alzheimer's disease (AD) dementia. Recent imaging-pathologic association studies suggest TDP-43/HS linked to distinct neurodegeneration pattern may be used detect the condition in-vivo. From ADNI autopsy cohort we identified 41 patients clinical diagnosis of MCI or AD dementia at last evaluation availability an FDG-PET scan. Six (15%) had limbic but low pathology, two whom also HS. Seventeen showed typical without co-morbid TDP-43/HS. "TDP-43-typical" "AD-typical" hypometabolic patterns were estimated by contrasting data respective groups normative from healthy older controls (N=179). The pathology-specific classify individual larger samples (N=251) aMCI (N=403) based on spatial correlation approach provides "AD/TDP-43-index" whether scan more "AD-like" "TDP-43-like". tested for associations clinical, molecular biomarker, genetic features using dichotomous comparisons between classified patient as well analyses AD/TDP-43-index continuous variable. Compared AD-typical hypometabolism, TDP-43-typical pronounced involvement temporolimbic frontal areas less posterior temporo-parietal (Fig.1). Clinically diagnosed TDP-43-like (N=26, 10%) did not differ significantly global cognition memory scores AD-like pattern, impaired executive functions severe cognitive decline over follow-up (p<0.01). They older, lower levels amyloid-β tau biomarkers, APOE4 allele frequency, higher frequency TMEM106B risk (all p<0.01). hypometabolism similar characteristics, all results remained significant when analyzing expression scale.