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

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

Author information

1
Section for Dementia Research, Hertie-Institute of Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany. Electronic address: christoph.laske@med.uni-tuebingen.de.
2
Department of Cardiology, Centre of Internal Medicine III, Goethe University, Frankfurt am Main, Germany; Vascular Inflammation Group, Institute of Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
3
Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
4
Section for Dementia Research, Hertie-Institute of Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
5
DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany; Department of Neurodegeneration, Center of Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.

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

PMID:
25200336
DOI:
10.1016/j.jalz.2014.06.003
[Indexed for MEDLINE]

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