Cortical microstructural correlates of astrocytosis in autosomal-dominant Alzheimer disease
Vilaplana, Eduard (Institut d'Investigació Biomèdica Sant Pau)
Rodriguez-Vieitez, Elena (Institut d'Investigació Biomèdica Sant Pau)
Ferreira, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Montal, Victor (Institut d'Investigació Biomèdica Sant Pau)
Almkvist, Ove (Institut d'Investigació Biomèdica Sant Pau)
Wall, Anders (Institut d'Investigació Biomèdica Sant Pau)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Westman, Eric (Institut d'Investigació Biomèdica Sant Pau)
Graff, Caroline (Institut d'Investigació Biomèdica Sant Pau)
Fortea, Juan (Institut d'Investigació Biomèdica Sant Pau)
Nordberg, Agneta (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	To study the macrostructural and microstructural MRI correlates of brain astrocytosis, measured with 11 C-deuterium-L-deprenyl (11 C-DED)-PET, in familial autosomal-dominant Alzheimer disease (ADAD). The total sample (n = 31) comprised ADAD mutation carriers (n = 10 presymptomatic, 39. 2 ± 10. 6 years old; n = 3 symptomatic, 55. 5 ± 2. 0 years old) and noncarriers (n = 18, 44. 0 ± 13. 7 years old) belonging to families with mutations in either the presenilin-1 or amyloid precursor protein genes. All participants underwent structural and diffusion MRI and neuropsychological assessment, and 20 participants (6 presymptomatic and 3 symptomatic mutation carriers and 11 noncarriers) also underwent 11 C-DED-PET. Vertex-wise interaction analyses revealed a differential relationship between carriers and noncarriers in the association between 11 C-DED binding and estimated years to onset (EYO) and between cortical mean diffusivity (MD) and EYO. These differences were due to higher 11 C-DED binding in presymptomatic carriers, with lower binding in symptomatic carriers compared to noncarriers, and to lower cortical MD in presymptomatic carriers, with higher MD in symptomatic carriers compared to noncarriers. Using a vertex-wise local correlation approach, 11 C-DED binding was negatively correlated with cortical MD and positively correlated with cortical thickness. Our proof-of-concept study is the first to show that microstructural and macrostructural changes can reflect underlying neuroinflammatory mechanisms in early stages of Alzheimer disease (AD). The findings support a role for neuroinflammation in AD pathogenesis, with potential implications for the correct interpretation of neuroimaging biomarkers as surrogate endpoints in clinical trials.
Note:	Altres ajuts: This work was financially supported by grants from the Swedish Research Council (projects 2017-02965, 2017-06086, K2014-61×-05817), the Swedish Foundation for Strategic Research (SSF, project RB13-0192), the Knut and Alice Wallenberg Foundation, the Stockholm County Council-Karolinska Institutet regional agreement on medical training and clinical research (ALF grant), GE Healthcare (unrestricted grant), the Swedish Brain Foundation, the Alzheimer Foundation in Sweden, the Dementia Association, Swedish Brain Power, the EU FP7 large-scale integrating project INMiND (uni-muenster.de/INMiND), the Foundation for Old Servants, Karolinska Institutet's Foundation for Aging Research, Gun and Bertil Stohne's Foundation, Loo and Hans Osterman's Foundation, the Åhlén Foundation, the Åke Wiberg Foundation, and the Departament de Salut de la Generalitat de Catalunya, Pla estratègic de recerca i innovació en salut (PERIS) 2016-2020 (SLT006/17/95).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Neurology, Vol. 94 (may 2020) , p. e2026-e2036, ISSN 1526-632X

DOI: 10.1212/WNL.0000000000009405
PMID: 32291295

11 p, 572.5 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles