title: Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer's disease subjects.
abstract: Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidation, and ketogenesis has been found to be decreased on aging. Furthermore, in elderly subjects, alterations in plasma levels of specific ACCs have been suggested to predict conversion to mild cognitive impairment (MCI) or AD. In this study, we assayed plasma profiles of ACCs in a cohort of healthy elderly control, MCI subjects, and AD patients. Compared with healthy controls or MCI subjects, AD patients showed significant lower plasma levels of several medium-chain ACCs. Furthermore, in AD patients, these lower concentrations were associated with lower prefrontal gray matter volumes and the presence of cognitive impairment. Interestingly, lower levels of medium-chain ACCs were also found to be associated with lower plasma levels of 2-hydroxybutyric acid. Overall, these findings suggest that altered metabolism of medium-chain ACCs and impaired ketogenesis can be metabolic features of AD.
authors.affiliation: School of Human and Social Science, "Kore" University of Enna, Enna, Italy; Molecular Neurology Unit, Center of Excellence on Aging and Translational Medicine (Ce.S.I.-MeT), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ciavardelli
authors.affiliation: Department of Clinical and Behavioral Neurology, Neuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; "Enrico Fermi" Centre for Study and Research, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Piras
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, ''G. d'Annunzio'' University of Chieti-Pescara, Chieti, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Consalvo
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, ''G. d'Annunzio'' University of Chieti-Pescara, Chieti, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rossi
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, ''G. d'Annunzio'' University of Chieti-Pescara, Chieti, Italy.
authors.forename: Mirco
authors.initials: M
authors.lastname: Zucchelli
authors.affiliation: Department of Medical, Oral, and Biotechnological Sciences, ''G. d'Annunzio'' University of Chieti-Pescara, Chieti, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Di Ilio
authors.affiliation: Molecular Neurology Unit, Center of Excellence on Aging and Translational Medicine (Ce.S.I.-MeT), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Frazzini
authors.affiliation: Department of Clinical and Behavioral Neurology, Neuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Neuroscience, University "Tor Vergata", Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Department of Clinical and Behavioral Neurology, Neuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
authors.affiliation: Molecular Neurology Unit, Center of Excellence on Aging and Translational Medicine (Ce.S.I.-MeT), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy; Department of Neurology, and Institute for Memory Impairments and Neurological Disorders, University of California-Irvine, Irvine, CA, USA; Department of Pharmacology, and Institute for Memory Impairments and Neurological Disorders, University of California-Irvine, Irvine, CA, USA. Electronic address: ssensi@uci.edu.
authors.forename: Stefano L
authors.initials: SL
authors.lastname: Sensi
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood* / Q000473:pathology / Q000523:psychology*; D000544:Alzheimer Disease / Q000097:blood / Q000469:parasitology* / Q000473:pathology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000097:blood* / Q000473:pathology / Q000523:psychology*; D015331:Cohort Studies; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007657:Ketone Bodies / Q000097:blood*; D008297:Male
chemical_list: D006885:Hydroxybutyrates; D007657:Ketone Bodies; C116917:acylcarnitine; C031570:2-hydroxybutyric acid; D002331:Carnitine
keywords: Cognitive decline; Fatty acid beta-oxidation; Ketogenesis; Medium-chain acylcarnitines; Targeted metabolomics