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CSF 7‐ketocholesterol is related to β‐amyloid and white matter microstructure in healthy adults
Author(s) -
Iriondo Ane,
GarciaSebastian Maite,
Arrospide Arantzazu,
Arriba Maria,
Aurtenetxe Sara,
Barandiaran Myriam,
Clerigue Montserrat,
Ecay Mirian,
Estanga Ainara,
Gabilondo Alazne,
Izagirre Andrea,
Saldias Jon,
Tainta Mikel,
Villanua Jorge A,
Blennow Kaj,
Zetterberg Henrik,
Mar Javier,
AbadGarcía Beatriz,
Dias Irundika,
Goñi Félix María,
MartinezLage Pablo
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041015
Subject(s) - fornix , fractional anisotropy , corpus callosum , splenium , white matter , diffusion mri , cognitive decline , medicine , psychology , endocrinology , neuroscience , pathology , dementia , hippocampus , disease , magnetic resonance imaging , radiology
Background Abnormal cholesterol metabolism changes the neuronal membrane and interferes with amyloidogenesis. Oxysterols in CSF are related to Alzheimer’s disease (AD) biomarkers in mild cognitive impairment and dementia. Cholesterol turnover is important for axonal and white matter (WM) microstructure maintenance. We aim to demonstrate that the association of oxysterols, biomarkers and WM microstructure occurs early in asymptomatic individuals. Method We studied the association of inter‐individual variability of CSF 24‐hydroxycholesterol (24‐OHC), 27‐hydroxycholesterol (27‐OHC), 7‐ketocholesterol (7‐KC), 7β‐hydroxycholesterol (7β‐OHC), β‐amyloid 1‐42 (Aβ 42 ), total‐tau (t‐tau), phosphorylated‐tau (p‐tau), neurofilament (NfL) and WM microstructure in cognitive regions, using diffusion tensor imaging (DTI), generalized lineal models and moderation/mediation analyses in 153 healthy adults. Result 7‐KC levels were related to Aβ 42 ( B = ‐1.41; p = 0.041) . Higher 7‐KC levels were related to lower fractional anisotropy (FA) and higher mean (MD), axial (AxD) and radial (RD) diffusivity in cognitive regions. 7‐KC modulated the association between AxD and NfL in the corpus callosum splenium ( B = 39.39, p = 0.017) and genu ( B = 68.64, p = 0.000) and fornix ( B = 10.97, p = 0.000). Lower Aβ 42 levels were associated to lower FA and higher MD, AxD and RD in the fornix, corpus callosum, inferior longitudinal fasciculus and hippocampus. The association between AxD and Aβ 42 was moderated by 7K‐C (p= 0.048). Conclusion This study adds clinical evidence to support the role of 7K‐C on axonal integrity and the involvement of cholesterol metabolism in the Aβ 42 generation process.