APOE ε4 gene dose effect on imaging and blood biomarkers of glial reactivity and β-amyloid pathology

Snellman, A.; Ekblad, L. L.; Tuisku, J.; Koivumäki, M.; Ashton, N. J.; Lantero-Rodriguez, J.; Karikari, T. K.; Helin, S.; Bucci, M.; Löyttyniemi, E.; Parkkola, R.; Karrash, M.; Schöll, M.; Zetterberg, H.; Blennow, K.; Rinne, J.

doi:10.1101/2022.09.19.508484

bioRxiv · 10.1101/2022.09.19.508484

APOE ε4 gene dose effect on imaging and blood biomarkers of glial reactivity and β-amyloid pathology

Snellman, A.·Ekblad, L. L.·Tuisku, J.·Koivumäki, M.·Ashton, N. J.·Lantero-Rodriguez, J.·Karikari, T. K.·Helin, S.·Bucci, M.·Löyttyniemi, E.·Parkkola, R.·Karrash, M.·Schöll, M.·Zetterberg, H.·Blennow, K.·Rinne, J.

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Abstract

Increased reactivity of microglia and astrocytes is known to be present at various stages of the Alzheimers continuum but their relationship with core Alzheimers disease pathology in the preclinical stages is less clear. We investigated glial reactivity and {beta}-amyloid pathology in cognitively unimpaired APOE {varepsilon}4 homozygotes, heterozygotes and non-carriers using 11C-PK11195 PET (targeting 18-kDa translocator protein), 11C-PiB PET (targeting {beta}-amyloid), brain MRI, and a preclinical cognitive composite (APCC). Plasma glial fibrillary acidic protein (GFAP) by and plasma A{beta}1-42/1-40 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 {varepsilon}4 homozygotes compared with non-carriers in all evaluated regions, (ii) regional 11C-PK11195-binding did not differ between the APOE {varepsilon}4 gene doses or between A{beta}-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 Alzheimers disease in parallel with early neurodegenerative changes.

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Snellman, A., Ekblad, L. L., Tuisku, J., Koivumäki, M., Ashton, N. J., Lantero-Rodriguez, J., Karikari, T. K., Helin, S., Bucci, M., Löyttyniemi, E., Parkkola, R., Karrash, M., Schöll, M., Zetterberg, H., Blennow, K., Rinne, J.. 2022-09-20. APOE ε4 gene dose effect on imaging and blood biomarkers of glial reactivity and β-amyloid pathology. https://doi.org/10.1101/2022.09.19.508484

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