• Guozhen Qiu, Chunyan Xu, Qiwen Guo, and Fei-Qi Zhu.
• The Third Affiliated Hospital of Shenzhen University, Cognitive Impairment Ward of Neurology Department, Shenzhen, Guangdong Province, China.
• Medicine (Baltimore). 2021 Apr 23; 100 (16): e25585e25585.

RationaleThe sortilin-related receptor 1 gene (SORL1) encodes a key protein (SORLA) involved in the pathophysiology of Alzheimer disease (AD). SORLA also mediates a trophic pathway that acts through glial cell line-derived neurotrophic factor (GDNF), a critical survival factor for the midbrain dopaminergic (DA) neurons.Patient ConcernsFour patients presented to our hospital with complaints of progressive memory decline, who developed extrapyramidal signs (EPS) and psychiatric symptoms.DiagnosesAll 4 patients were diagnosed with AD based on their symptoms, findings from cranial magnetic resonance imaging, and cerebrospinal fluid analysis.InterventionsWe also performed whole-exome sequencing (WES) and found 4 novel mutations in SORL1. Donepezil, rivastigmine, memantine, madopar, quetiapine, and risperidone were administrated as therapy.OutcomesThe four mutations would change the thermal stability of SORLA domain. This could be associated with parkinsonian and psychiatric features in AD. These patients showed improvements in parkinsonian and psychiatric features.LessonsThese cases suggest that SORL1 mutations might result in aggregation of a-synuclein through altered function of GDNF and further lead to appearance of core dementia with Lewy bodies features.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

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