With the global prevalence of 0.1–9.6 in every 100,000 individuals, based on geographical location [114], HSP is mainly observed in AD pure form in about 80% of the North American and north European HSP populations, with SPG4/SPAST mutations in 40%, SPG3A/ATL1 mutations in 10% at HSPs’ early beginning, about 10% SPG31/REEP1 mutations, and almost 3% SPG10/KIF5A mutations [114,115]. Here, ATL1 is linked to Alzheimer disease.