Targeted proteomics in Alzheimer’s disease: focus on amyloid-β

Abstract

Diagnosis and monitoring of sporadic Alzheimer’s disease (AD) have long depended on clinical examination of individuals with end-stage disease. However, upcoming anti-AD therapies are optimally initiated when individuals show very mild signs of neurodegeneration. There is a developing consensus for cerebrospinal fluid amyloid-β (Aβ) as a core biomarker for the mild cognitive impairment stage of AD. Aβ is directly involved in the pathogenesis of AD or tightly correlated with other primary pathogenic factors. It is produced from amyloid precursor protein (APP) by proteolytic processing that depends on the β-site APP-cleaving enzyme 1 and the γ-secretase complex, and is degraded by a broad range of proteases. This review summarizes targeted proteomic studies of Aβ in biological fluids and identifies clinically useful markers of disrupted Aβ homeostasis in AD. The next 5 years will see a range of novel assays developed on the basis of these results. From a longer perspective, establishment of the most effective combinations of different biomarkers and other diagnostic modalities may be foreseen.

Keywords::

• Alzheimer’s disease
• amyloid β
• biomarker
• cerebrospinal fluid
• mass spectrometry
• oligomer
• proteomics

Financial & competing interests disclosure

This work was supported by grants from the Swedish Medical Research Council (projects 2006-2740 and 2006-6227), the Sahlgrenska University Hospital, the Göteborg Medical Society, Stiftelsen Gamla Tjänarinnor, Pfannenstills stiftelse, Alzheimer Foundation, Sweden. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.