Alzheimer disease biomarker profiles in dementia with Lewy bodies

Abstract

The advent of biofluid and molecular imaging biomarkers to reliably detect Alzheimer disease (AD) neuropathology in vivo has led to the increasing recognition of the complexity of clinicopathologic associations in neurodegenerative disease. For example, the clinical syndrome of dementia with Lewy bodies (DLB)1 is relatively specific to identify individuals with dementia due to underlying neocortical α-synuclein “Lewy” pathology; however, the majority of patients with DLB have sufficient additional plaque and tangle pathology at autopsy for a secondary diagnosis of AD neuropathologic change associated with poor clinical outcomes.2 Moreover, at least 50% of patients with clinical AD have additional α-synuclein pathology at autopsy.2 Thus, there is a current paradigm shift to define AD and related neurodegenerative disorders in living patients on a biological basis, rather than on a syndromic one alone. This is exemplified by the recent National Institute on Aging/Alzheimer’s Association (NIA/AA) research framework3 for biomarker classification of patients based on categorical biomarker evidence for β-amyloid plaque (A), tau neurofibrillary tangles (T), and resultant neurodegeneration (N); i.e., A/T(N) classification scheme. The purpose of this approach is to provide a common nomenclature to test hypotheses on the biological underpinnings of neurodegenerative disorders and to improve therapeutic trials by creating more biologically homogenous cohorts.3 In this issue of Neurology ®, Ferreira et al.4 apply and test clinical associations of A/T biomarker profiles in a large international cohort of 417 patients with DLB from 10 centers in the European DLB Consortium and from the Mayo Clinic.