PSEN2 and ABCA7 variants causing early-onset preclinical pathological changes in Alzheimer's disease: a case report and literature review

BackgroundAlzheimer's disease (AD) is a debilitating and highly heritable neurodegenerative disease. Early-onset AD (EOAD) was defined as AD occurring before age 65. Although it has a high genetic risk, EOAD due to PSEN2 variation is very rare. ABCA7 is an important risk gene for AD. Previously reported cases mainly carried variations in a single pathogenic or risk gene.Methods and ResultsIn this study, we report a 35-year-old female carrying variants in both the PSEN2 gene (c.640G > T p.V214L) and ABCA7 gene (c.2848G > A p.V950M). Four previously reported cases carried PSEN2 V214L, and no reported cases carried ABCA7 V950M. She had a history of migraine, patent foramen ovale, spontaneous subarachnoid hemorrhage without aneurysm, and multiple cerebral microhemorrhages. Her MMSE score was 24/30, and her MoCA score was 22/30. The concentration of A beta 42 and the ratio of A beta 42 to A beta 40 in cerebral spinal fluid were obviously decreased. Published variants of PSEN2 and ABCA7 in PubMed were reviewed, and the patients' characteristics were summarized and compared to provide information for the clinical diagnosis of AD.ConclusionsIt is necessary to conduct genetic screening in cases with atypical manifestations.

Automated summary

This study reported a 35-year-old female with variants in both the PSEN2 and ABCA7 genes. She had a history of migraine, patent foramen ovale, spontaneous subarachnoid hemorrhage, and multiple cerebral microhemorrhages. The findings provide information for the clinical diagnosis of AD through reviewing and comparing the published variants of PSEN2 and ABCA7 in PubMed.