Diagnosis of AD has developed from a pathological approach to a more clinical and exclusionary approach.1,3 NIA-AA Criteria published in 2011, combined with a clinical and biological approach developed by the International Working Group (IWG), allowed for the emergence of a clinical diagnosis.3,16,17 Subsequent efforts by the National Institute on Aging and the Alzheimer’s Association working groups incorporated biomarkers, working towards a purely biological categorization of AD.18,19 The Braak staging system, developed in 1991, provides the ability to differentiate multiple disease phases based on the anatomical distribution of changes in neuropathology.5,20 More recently, blood phosphorylated tau (p-tau)181, p-tau217, and p-tau231 biomarkers reflecting brain tau and amyloid-b (Ab) pathology have been developed.12 The availability of blood-based biomarkers provides potential benefit over CSF or PET biomarkers owing to a less invasive, and more flexible, time- and cost-saving approach.12 Blood-based biomarkers allow for improved AD pre-screening, more definitive and differential diagnosis, and use in population-based and epidemiological studies.12 In 2021, the FDA accelerated the approval of aducanumab for treatment of AD, making it the first novel therapy approved for AD since 2003 and the first treatment to target underlying pathophysiology of AD – Ab plaques.13 In 2023, the FDA granted traditional approval to lecanemab as another treatment option to target the underlying disease process of AD, rather than solely treating symptoms.15 Considerable advancements in AD research have been made over the years, working towards a reality of early identification and multimodal treatment of patients with AD.21 In July 2023, positive results of a Phase 3 randomized clinical trial of donanemab in early symptomatic AD were published.14 In addition, there are currently several disease-modifying treatments being investigated, such as agents targeting amyloid accumulation, tau pathology, and others.22
References:
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