Alzheimer’s disease (AD) is the most common cause of dementia. The well-established biomarkers of AD in cerebrospinal fluid (CSF) are: amyloid β1‑42 (Aβ1‑42), total-tau protein (T-tau) and phosphorylated tau (p-tau). These best validated CSF biomarkers are useful in the diagnosis and prediction of AD dementia, however they are not entirely specific for AD. Novel biomarkers that will allow for early recognition of an ongoing pathological process are critically needed in the diagnosis of AD patients. Some clinical investigations have proved that matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in the pathology of central nervous system, including AD. The presence of MMPs and their tissue inhibitors was found around amyloid plaques and neurofibrillary tangles. MMPs play an important role in the extracellular amyloid beta catabolism and may contribute to AD pathogenesis via a disruption of the blood brain barrier. Limited proteolysis of tau protein by MMP-9 increases tau oligomer formation. An assessment of functional relationship between the presence of the beta-amyloid peptide and the synthesis of inflammatory mediators within the amyloid plaques may be helpful to better understanding of the pathological mechanism of AD. Other novel biomarkers of AD are visinin-like protein 1 (VILIP‑1), chitinase‑3‑like protein 1 (YKL‑40) and selected Aβ isoforms. VILIP-1 is an indicator of neurodegeneration, while YKL‑40 is a biomarker of neuroinflammation. It has been shown that ratios of Aβ isoforms (Aβ42/Aβ40 and Aβ42/Aβ38) may be useful in the discrimination between AD and non-AD MCI. The combined use of novel biomarkers with well-known CSF biomarkers could improve AD diagnostics and result in a higher level of sensitivity and diagnostic accuracy for discrimination between AD and patients with other neurological dementia disorders. FINANCIAL SUPPORT: Financial support: This study was supported by the Leading National Research Centre (KNOW) and grants for neurodegenerative diseases, Medical University of Białystok, Poland. The study was conducted with the use of equipment purchased by Medical University of Białystok as part of the RPOWP 2007–2013 funding, Priority I, Axis 1.1, contract No. UDA-RPPD.01.01.00-20-001/15-00 dated 26.06.2015.
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