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

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Abstract

Background

Alzheimer’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 Results

In 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 Aβ42 and the ratio of Aβ42 to Aβ40 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.

Conclusions

It is necessary to conduct genetic screening in cases with atypical manifestations.

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Data availability

The raw data presented in this article will be available by the authors, and reasonable requests to access the datasets should be directed to the corresponding author after legal permission.

Code availability

Not applicable.

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Author notes

  1. Jiale Gan and Hui Zhou equally contributed to the work.

Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, China

    Jiale Gan, Hui Zhou & Liangjuan Fang

  2. Ningxia Hospital of Traditional Chinese Medicine, Ningxia, China

    Jiale Gan & Chao Liu

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  1. Jiale Gan
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  2. Hui Zhou
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  3. Chao Liu
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Correspondence to Liangjuan Fang.

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The study involving human participants was reviewed and approved by the Ethics Committee of Xiangya Hospital of Central South University.

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Gan, J., Zhou, H., Liu, C. et al. PSEN2 and ABCA7 variants causing early-onset preclinical pathological changes in Alzheimer's disease: a case report and literature review. Neurol Sci 44, 1987–2001 (2023). https://doi.org/10.1007/s10072-023-06602-5

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