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Research paper
CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer's disease
  1. C Liguori1,2,
  2. A Stefani2,3,
  3. G Sancesario2,3,
  4. G M Sancesario4,
  5. M G Marciani2,3,
  6. M Pierantozzi2
  1. 1Department of Systems Medicine, Neurophysiopathology Unit, University of Rome “Tor Vergata”, Rome, Italy
  2. 2Department of Systems Medicine, Neurology Unit, University of Rome “Tor Vergata”, Rome, Italy
  3. 3Fondazione Santa Lucia IRCCS, Rome, Italy
  4. 4Department of Clinical Biochemistry and Molecular Biology, University of Rome “Tor Vergata”, Rome, Italy
  1. Correspondence to Dr Claudio Liguori, Department of Systems Medicine, Neurophysiopathology Unit, University of Rome “Tor Vergata”, Viale Oxford 81 Rome 00133, Italy; dott.claudioliguori{at}yahoo.it

Abstract

Objectives 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.

  • ALZHEIMER'S DISEASE

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