It is interesting that several ephrin proteins, including EFNB2, EPHA3 and EPHB2 (28), and SNCA, the major hallmark of all synucleinopathies, accumulate in Purkinje cells in different neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and Alzheimer's disease (AD) (34–37), suggesting that they are critical for synaptic homeostasis in ARSACS. This evidence concerns the gene EPHB2 and early-onset autosomal dominant Alzheimer disease.