title: CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer's disease.
abstract: OBJECTIVE
  To investigate, in patients with Alzheimer's Disease (AD), the possible interplay linking alteration of neuronal energy metabolism, as measured via cerebrospinal fluid (CSF) lactate concentration, to severity of AD neurodegenerative processes and impairment of cognitive abilities.
  
  
  METHODS
  In this study we measured and correlated CSF lactate concentrations, AD biomarker levels (τ-proteins and β-amyloid) and Mini-Mental State Examination (MMSE) score in a population of drug-naïve patients with AD ranging from mild (MMSE≥21/30) to moderate-severe (MMSE<21/30) cognitive decline. They were compared to healthy controls and patients with vascular dementia (VaD).
  
  
  RESULTS
  Patients with AD (n=145) showed a significant increase of CSF lactate concentration compared to controls (n=80) and patients with VaD (n=44), which was higher in mild (n=67) than in patients with moderate-severe AD (n=78). Moreover, we found, in either the whole AD population or both subgroups, a CSF profile in which higher CSF levels of t-τ and p-τ proteins corresponded to lower concentrations of lactate.
  
  
  CONCLUSIONS
  We verified the occurrence of high CSF lactate levels in patients with AD, which may be ascribed to mitochondria impairment. Hypothesising that τ proteins may exert a detrimental effect on the entire cellular energy metabolism, the negative correlation found between lactate and τ-protein levels may allow speculation that τ toxicity, already demonstrated to have affected mitochondria, could also impair glycolytic metabolism with a less evident increase of lactate levels in more severe AD. Thus, we suggest a dynamic relationship between neuronal energy metabolism, τ proteins and cognitive decline in AD and propose the clinical potential of assessing CSF lactate levels in patients with AD to better define the neuronal brain metabolism damage.
authors.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, University of Rome "Tor Vergata", Rome, Italy Department of Systems Medicine, Neurology Unit, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Liguori
authors.affiliation: Department of Systems Medicine, Neurology Unit, University of Rome "Tor Vergata", Rome, Italy Fondazione Santa Lucia IRCCS, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Stefani
authors.affiliation: Department of Systems Medicine, Neurology Unit, University of Rome "Tor Vergata", Rome, Italy Fondazione Santa Lucia IRCCS, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sancesario
authors.affiliation: Department of Clinical Biochemistry and Molecular Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: G M
authors.initials: GM
authors.lastname: Sancesario
authors.affiliation: Department of Systems Medicine, Neurology Unit, University of Rome "Tor Vergata", Rome, Italy Fondazione Santa Lucia IRCCS, Rome, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Marciani
authors.affiliation: Department of Systems Medicine, Neurology Unit, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pierantozzi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000523:psychology*; D015140:Dementia, Vascular / Q000134:cerebrospinal fluid / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000134:cerebrospinal fluid*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019344:Lactic Acid
keywords: ALZHEIMER'S DISEASE