Development of molecular tools for diagnosis of Alzheimer’s disease that are based on detection of amyloidogenic proteins

ABSTRACT Alzheimer’s disease (AD) is the most common form of dementia that usually occurs among older people. AD results from neuronal degeneration that leads to the cognitive impairment and death. AD is incurable, typically develops over the course of many years and is accompanied by a loss of functional autonomy, making a patient completely dependent on family members and/or healthcare workers. Critical features of AD are pathological polymerization of Aβ peptide and microtubule-associated protein tau, accompanied by alterations of their conformations and resulting in accumulation of cross-β fibrils (amyloids) in human brains. AD apparently progresses asymptomatically for years or even decades before the appearance of symptoms. Therefore, development of the early AD diagnosis at a pre-symptomatic stage is essential for potential therapies. This review is focused on current and potential molecular tools (including non-invasive methods) that are based on detection of amyloidogenic proteins and can be applicable to early diagnosis of AD. Abbreviations: Aβ – amyloid-β peptide; AβO – amyloid-β oligomers; AD – Alzheimer’s disease; ADRDA – Alzheimer’s Disease and Related Disorders Association; APH1 - anterior pharynx defective 1; APP – amyloid precursor protein; BACE1 – β-site APP-cleaving enzyme 1; BBB – brain blood barrier; CJD - Creutzfeldt-Jakob disease; CRM – certified reference material; CSF – cerebrospinal fluid; ELISA – enzyme-linked immunosorbent assay; FGD – 18F-fluorodesoxyglucose (2-deoxy-2-[18F]fluoro-D-glucose); IP-MS – immunoprecipitation-mass spectrometry assay; MCI – mild cognitive impairment; MDS – multimer detection system; MRI – magnetic resonance imaging; NIA-AA – National Institute on Ageing and Alzheimer’s Association; NINCDS – National Institute of Neurological and Communicative Disorders and Stroke; PEN2 – presenilin enhancer 2; PET – positron emission tomography; PiB – Pittsburgh Compound B; PiB-SUVR - PIB standardized uptake value ratio; PMCA – Protein Misfolding Cycling Amplification; PrP – Prion Protein; P-tau – hyperphosphorylated tau protein; RMP – reference measurement procedure; RT-QuIC - real-time quaking-induced conversion; SiMoA – single-molecule array; ThT – thioflavin T; TSEs – Transmissible Spongiform Encephslopathies; T-tau – total tau protein