PSEN2 and ABCA7 Variants Causing Early-onset Preclinical Pathological Changes in Alzheimer's Disease: a Case Report and Literature Review

Overview

Journal Neurol Sci

Specialty Neurology

Date 2023 Jan 26

PMID 36701017

Authors

Jiale Gan

Hui Zhou

Chao Liu

Liangjuan Fang

Affiliations

Soon will be listed here.

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.

Citing Articles

Identification and characterization of variants in PSEN1, PSEN2, and APP genes in Chinese patients with early-onset Alzheimer's disease.

Nan H, Chu M, Jiang D, Liang W, Li Y, Wu Y Alzheimers Res Ther. 2025; 17(1):54.

PMID: 40016812 PMC: 11866898. DOI: 10.1186/s13195-025-01702-0.

Case report: Double mutations in a patient with early-onset Alzheimer's disease in China, PSEN2 and IDE variants.

Chang Z, Wang Z, Luo L, Xie Z, Yue C, Bian X Front Neurosci. 2024; 18:1423892.

PMID: 39539495 PMC: 11557526. DOI: 10.3389/fnins.2024.1423892.

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