The biological diagnosis of Alzheimer's disease using blood-based biomarkers: a Canadian prospective

Dementia is the most common type of neurodegenerative disease, with Alzheimer's Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling from 2011. The total annual economic burden of dementia in Canada was about $40 billion in 2020, with an approximate average of $67,200 per person with dementia and if current trends continue, its annual burden could grow by 275 % over 30 years. AD is a double proteinopathy with its fundamental neuropathologic features defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles with aggregated tau proteins. This supports the potential for mechanism-based proteomic biomarkers to be detected in biofluids. Pathophysiologic and topographical biomarkers have significantly improved the diagnosis of typical and atypical phenotypes of AD, helping clinicians recognize and differentiate AD phenotypes from other types of dementia and neurodegenerative diseases. The cerebrospinal fluid Aβ42/Aβ40 ratio measurement is a robust biomarker in detecting cerebral Aβ pathology and AD diagnosis. A number of very sensitive assays for measuring AD blood biomarkers including p-tau217, front-runner candidate for AD diagnosis, have been developed during last years. In this review we discuss the biological configuration and normal function of involved proteomics in AD including Aβ and tau protein, particularly tau phosphorylation and biochemistry of tau isoforms and their detection feasibility in plasma using novel technologies. Then, we critically review blood-based biomarkers' analytical and clinical validations, focusing more on plasma p-tau217 and their availability and prospects in Canada.