Increased cerebrospinal fluid calpain activity and microparticle levels in Alzheimer's disease

Alzheimers Dement. 2015 May;11(5):465-74. doi: 10.1016/j.jalz.2014.06.003. Epub 2014 Sep 4.

Abstract

Background: Calpain has been associated with the pathophysiology of Alzheimer's disease (AD) and with apoptotic neuronal cell death leading to microparticles (MPs) formation.

Methods: A total of 64 patients with AD and 52 age- and gender-matched cognitively healthy elderly controls were included in the study. We measured calpain activity and levels of MPs, amyloid beta (Aβ1-42), h-tau, and p-tau181.

Results: AD patients showed significantly increased calpain activity and higher levels of MPs in cerebrospinal fluid (CSF) and significantly decreased calpain activity and lower levels of MPs in serum and plasma compared with healthy controls. Combined assessment of calpain activity and Aβ1-42 levels in CSF improved diagnostic accuracy as compared with singular or combined traditional CSF biomarkers of AD.

Conclusions: This is the first study showing increased calpain activity and microparticle levels in CSF of AD patients. Calpain activity could represent a novel diagnostic and prognostic biomarker and promising treatment target for AD.

Keywords: Alzheimer's disease; CSF; Calpain activity; Dementia; Microparticles; Plasma; Serum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid*
  • Calpain / blood
  • Calpain / cerebrospinal fluid*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Psychiatric Status Rating Scales
  • Statistics, Nonparametric
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Calpain