RT Journal Article SR Electronic T1 APOE ε4 gene dose effect on imaging and blood biomarkers of glial reactivity and β-amyloid pathology JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.09.19.508484 DO 10.1101/2022.09.19.508484 A1 Anniina Snellman A1 Laura L. Ekblad A1 Jouni Tuisku A1 Mikko Koivumäki A1 Nicholas J. Ashton A1 Juan Lantero-Rodriguez A1 Thomas K. Karikari A1 Semi Helin A1 Marco Bucci A1 Eliisa Löyttyniemi A1 Riitta Parkkola A1 Mira Karrasch A1 Michael Schöll A1 Henrik Zetterberg A1 Kaj Blennow A1 Juha O. Rinne YR 2022 UL http://biorxiv.org/content/early/2022/09/20/2022.09.19.508484.abstract AB Increased reactivity of microglia and astrocytes is known to be present at various stages of the Alzheimer’s continuum but their relationship with core Alzheimer’s disease pathology in the preclinical stages is less clear. We investigated glial reactivity and β-amyloid pathology in cognitively unimpaired APOE ε4 homozygotes, heterozygotes and non-carriers using 11C-PK11195 PET (targeting 18-kDa translocator protein), 11C-PiB PET (targeting β-amyloid), brain MRI, and a preclinical cognitive composite (APCC). Plasma glial fibrillary acidic protein (GFAP) by and plasma Aβ1-42/1-40 were measured using single molecule array and immunoprecipitation combined with mass spectrometry, respectively. We observed that (i) 11C-PiB-binding was significantly higher in APOE ε4 homozygotes compared with non-carriers in all evaluated regions, (ii) regional 11C-PK11195-binding did not differ between the APOE ε4 gene doses or between Aβ-positive and -negative individuals, and (iii) higher 11C-PK11195-binding and plasma GFAP were associated with lower hippocampal volume, and elevated 11C-PiB-binding and plasma GFAP concentration with lower APCC scores. Increased glial reactivity might emerge in later stages of preclinical Alzheimer’s disease in parallel with early neurodegenerative changes.Aβbeta-amyloid peptideAPOEApolipoprotein E geneApoEApolipoprotein ETSPO18-kDa translocator proteinGFAPGlial fibrillary acidic proteinGFAPglial fibrillary acidic proteinTSPO18-kDa translocator protein