Fig. 1.

Age-related neurodegenerative diseases display region-specific pathological patterns. Particular regions of the nervous system are selectively susceptible to degenerative decline in Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), however the mechanisms establishing the regionally restricted nature of age-related neurodegenerative diseases remain undefined. Indeed, regional pathological involvement of the hippocampus, substantia nigra pars compacta and ventral spinal cord determines major clinical and personal manifestations of AD, PD and ALS respectively, with important consequences for quality of life, healthspan and/or lifespan. There is an interplay between normal regional ageing and neurodegenerative disease pathology. Whether certain regions, such as the hippocampus, substantia nigra pars compacta and ventral spinal cord are more susceptible to age-associated alterations than other nervous system regions, which in turn renders them prone to disease-specific pathology, is reviewed in the main text. H = hippocampus; SN(pc) = substantia nigra (pars compacta); SpC = spinal cord. MN = motor neuron. Templates used/adapted to create this figure are freely available from Servier Medical Art (https://smart.servier.com/). (References used to create this figure: Bettio et al., 2017; Branch et al., 2014; Cenini and Voos, 2019; De Strooper and Karran, 2016; Hindle, 2010; Keller et al., 2000; Mu and Gage, 2011; Pandya and Patani, 2019; Penney et al., 2020; Piekarz et al., 2020; Reagh et al., 2018; Reeve et al., 2014; Trist et al., 2019; Van Damme et al., 2017).