Presymptomatic anterior frontal involvement in corticobasal degeneration.

Abstract

This scientific commentary refers to ‘Astrogliopathy predominates the earliest stage of corticobasal degeneration pathology’ by Ling et al. (doi:10.1093/brain/aww256) . One of the biggest challenges in the development of treatment for neurodegenerative disorders is being able to spot the earliest signs of disease, given that the underlying pathological changes may commence many years before clinical features develop. While models of pathological staging and spread have been established for common neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease, the pattern of presymptomatic spread of rarer conditions, such as the neurodegenerative tauopathy corticobasal degeneration (CBD), is less well characterized. In this issue of Brain , Ling et al. (2016) demonstrate early CBD pathology in three asymptomatic cases. The authors propose, by comparison with late-stage disease, that astroglial pathology dominates at this early stage, with an anterior–posterior gradient of pathological change in the frontal lobe during disease progression. The Braak staging system used in Alzheimer’s disease (Braak et al. , 2006) depicts a spread of tau pathology from medial temporal lobe structures to neocortical regions with disease progression. Similarly, current concepts of Parkinson’s disease indicate initial Lewy body pathology in the dorsal motor nucleus of the vagus and olfactory bulb, spreading to the midbrain and thereafter to neocortical structures (Braak et al. , 2003). Several factors have been crucial to the development of these staging systems. First, both conditions are relatively common, and the existence of monogenic inherited forms has allowed more accurate study of disease mechanisms and progression. Second, the identification of ‘presymptomatic’ features such as mild cognitive impairment, hyposmia and REM sleep behaviour disorder has enabled better understanding of disease evolution. Third, techniques such as amyloid-β PET imaging and the use of CSF biomarkers have permitted identification of early or presymptomatic disease. Indeed, in the case of Alzheimer’s disease, the …