Potential Biomarkers Found for Early Alzheimer's Diagnosis

The presymptomatic stage of Alzheimer’s disease (AD) occurs at least one decade before the clinical onset, highlighting the need for validated biomarkers that reflect this early period.

The success of future intervention strategies for AD will likely rely on the development of treatments, once a definitive diagnosis has been made early in the course of the disease, before irreversible brain damage occurs.

Scientists at Linköping University (Sweden) working with international collaborators, performed a targeted search for lysosomal network proteins in human cerebrospinal fluid (CSF). They studied samples of spinal marrow from 20 Alzheimer's patients and an equal number of healthy control subjects. The screening was aimed at 35 proteins that are associated with the lysosomal network.

CSF levels of the core AD biomarkers, including Aβ1–42, T-tau and P-tau181P phosphorylated at threonine181, were determined using INNOTEST enzyme linked immunosorbent assay (ELISA) kits (Innogenetics; Ghent, Belgium). Albumin levels were measured by immunonephelometry on a Beckman Image Immunochemistry system (Beckman Instruments, Beckman Coulter; Brea, CA, USA). Western blots were performed on CSF samples and immunodetection of the bound antibodies was performed using Amersham ECL detection systems (GE Healthcare; Pittsburgh, PA, USA).

Of thirty-four candidate lysosomal network proteins, they found that only six proteins were increased, indicating that a specific subset of lysosomal network proteins is overexpressed in the CSF of AD patients. The scientists identified the six as the endosomal proteins rat sarcoma (ras) in the brain 3, (Rab3) andRab7; the early endosomal antigen 1 (EEA1); the lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), and the autophagy microtubule-associated protein 1 light chain 3 (LC3) and all were significantly upregulated in the CSF of AD patients.

Katarina Kågedal, PhD, the lead author of the study said, “In victims of Alzheimer's, something happens to the lysosomes so that they can't manage to take care of the surplus of beta amyloid. They fill up with junk that normally is broken down into its component parts and recycled.” Her hope is that the group's discovery will contribute to early diagnoses of the illness, which is necessary in the first stage in order to be able to begin reliable clinical tests of candidates for drugs, but perhaps the six lysosomal proteins could also be targets for developing drugs. The study was published on October 8, 2013, in the journal Neuromolecular Medicine.

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Linköping University
Innogenetics
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