In contrast, massive synaptic degeneration was only observed in post-mortem tissue from terminal AD-ANCL patients (Fig. 6a, b) [5, 7], suggesting that the dysfunction in the soma of neurons likely at the lysosomal level occurs before the massive synaptic degeneration as a consequence of the aggregate-derived toxic effects of the mutation in DNAJC5/CSPα [16]. This evidence concerns the gene DNAJC5 and adult neuronal ceroid lipofuscinosis.