Protein Biomarker Improves Early Diagnosis of Alzheimer's Disease

The level of specific biomarkers in the plasma and cerebrospinal fluid (CSF) facilitates the early diagnosis of dementia in Alzheimer patients.

The biomarker, soluble circulating low-density lipoprotein receptor-related protein-1 (sLRP), provides key plasma binding activity for Alzheimer's disease (AD) amyloid-β peptide (Aβ).

Scientists at the University of Gothenburg (Gothenburg, Sweden) investigated the presence of sLRP in a total of 60 patients who were being investigated for dementia and took part in the study, along with 20 healthy controls. The study group included 14 patients with mild cognitive impairment (MCI) who progressed to AD (MCI-AD), 14 with AD, and 14 neurologically healthy controls. The investigators determined the amount of plasma oxidized sLRP and Aβ40/42 sLRP-bound, other proteins-bound and free plasma fractions, CSF tau/Aβ42 ratios, and mini-mental state examination (MMSE) scores in the study participants. The sLRP normally binds 70% - 90% of plasma Aβ preventing free Aβ access to the brain. In AD, Aβ binding to sLRP is compromised by increased levels of oxidized sLRP, which does not bind.

In MCI-AD patients prior to conversion to AD and AD patients, the increases in oxidized sLRP and free plasma Aβ40 and Aβ42 levels were 4.9 and 3.7-fold, 1.8, and 1.7-fold and 4.3 and 3.3-fold, respectively. In MCI-AD and AD patients, increases in oxidized sLRP and free plasma Aβ40 and Aβ42 correlated with increases in CSF tau/Aβ42 ratios and reductions in MMSE scores. The 24 patients who were considered as stable MCI patients were followed over a 2-4 years period had normal CSF tau/Aβ42 ratios, but increased oxidized sLRP levels.

The scientists concluded that these measurements could also be used to identify AD during the early stages of the disease. In such cases, the biomarkers can be used to identify those patients with mild symptoms who are most likely to benefit from treatment. The investigators also saw that patients who had not yet met all the clinical criteria for AD had similar levels of the biomarkers in their spinal fluid to patients who had developed the disease fully. The study was published in April 2011, in the Journal of Alzheimer's Disease.

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