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Lysosomal network proteins as potential novel CSF biomarkers for Alzheimer's disease.
- Source :
-
Neuromolecular medicine [Neuromolecular Med] 2014 Mar; Vol. 16 (1), pp. 150-60. Date of Electronic Publication: 2013 Oct 08. - Publication Year :
- 2014
-
Abstract
- The success of future intervention strategies for Alzheimer's disease (AD) will likely rely on the development of treatments starting early in the disease course, before irreversible brain damage occurs. The pre-symptomatic stage of AD occurs at least one decade before the clinical onset, highlighting the need for validated biomarkers that reflect this early period. Reliable biomarkers for AD are also needed in research and clinics for diagnosis, patient stratification, clinical trials, monitoring of disease progression and the development of new treatments. Changes in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are among the first alterations observed in an AD brain. In this study, we performed a targeted search for lysosomal network proteins in human cerebrospinal fluid (CSF). Thirty-four proteins were investigated, and six of them, early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were significantly increased in the CSF from AD patients compared with neurological controls. These results were confirmed in a validation cohort of CSF samples, and patients with no neurochemical evidence of AD, apart from increased total-tau, were found to have EEA1 levels corresponding to the increased total-tau levels. These findings indicate that increased levels of LAMP-1, LAMP-2, LC3, Rab3 and Rab7 in the CSF might be specific for AD, and increased EEA1 levels may be a sign of general neurodegeneration. These six lysosomal network proteins are potential AD biomarkers and may be used to investigate lysosomal involvement in AD pathogenesis.
- Subjects :
- Adult
Aged
Aged, 80 and over
Albumins cerebrospinal fluid
Amyloid beta-Peptides cerebrospinal fluid
Autophagy
Biomarkers cerebrospinal fluid
Endosomes chemistry
Female
Humans
Male
Middle Aged
Nerve Tissue Proteins cerebrospinal fluid
Peptide Fragments cerebrospinal fluid
Phagosomes chemistry
rab7 GTP-Binding Proteins
tau Proteins cerebrospinal fluid
Alzheimer Disease cerebrospinal fluid
Cerebrospinal Fluid Proteins cerebrospinal fluid
Lysosomal-Associated Membrane Protein 2 cerebrospinal fluid
Lysosomal Membrane Proteins cerebrospinal fluid
Lysosomes chemistry
Microtubule-Associated Proteins cerebrospinal fluid
Vesicular Transport Proteins cerebrospinal fluid
rab GTP-Binding Proteins cerebrospinal fluid
rab3 GTP-Binding Proteins cerebrospinal fluid
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1174
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neuromolecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 24101586
- Full Text :
- https://doi.org/10.1007/s12017-013-8269-3