title: Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging reveals cholesterol overload in the cerebral cortex of Alzheimer disease patients.
abstract: Although cholesterol has been involved in the pathophysiology of Alzheimer disease (AD), its distribution in the cerebral cortex over the course of AD is unknown. We describe an original method to quantify cholesterol distribution using time-of-flight secondary ion mass spectrometry imaging. Cholesterol was unevenly distributed along the cortical thickness, being more abundant close to the white matter, in both control and AD cases. However, the mean cholesterol signal was significantly higher in the lower half of the cortex in AD samples compared to controls. This increase, when converted into cortical layers, was statistically significant for layers III and IV and did not reach significance in layers V + VI, the variability being too high at the interface between grey and white matter. The density of neurofibrillary tangles and of senile plaques was not statistically linked to the abundance of cholesterol. Cholesterol overload thus appears a new and independent alteration of AD cerebral cortex. The structure in which cholesterol accumulates and the mechanism of this accumulation remain to be elucidated.
authors.affiliation: Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, 47 Bd de l'Hôpital, 75013 Paris, France.
authors.forename: Adina N
authors.initials: AN
authors.lastname: Lazar
authors.forename: Claudia
authors.initials: C
authors.lastname: Bich
authors.forename: Maï
authors.initials: M
authors.lastname: Panchal
authors.forename: Nicolas
authors.initials: N
authors.lastname: Desbenoit
authors.forename: Vanessa W
authors.initials: VW
authors.lastname: Petit
authors.forename: David
authors.initials: D
authors.lastname: Touboul
authors.forename: Luce
authors.initials: L
authors.lastname: Dauphinot
authors.forename: Catherine
authors.initials: C
authors.lastname: Marquer
authors.forename: Olivier
authors.initials: O
authors.lastname: Laprévote
authors.forename: Alain
authors.initials: A
authors.lastname: Brunelle
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D059906:Neuroimaging; D058225:Plaque, Amyloid; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods
chemical_list: D002784:Cholesterol