Very Early-Onset Alzheimer’s Disease in the Third Decade of Life with de novo PSEN1 Mutations

Article type: Short Communication

Authors: Chen, Ke-Liang^{a; 1} | Li, Pei-Xi^{a; 1} | Sun, Yi-Min^{a; 1} | Chen, Shu-Fen^a | Zuo, Chuan-Tao^b | Wang, Jian^a | Dong, Qiang^a | Cui, Mei^a | Yu, Jin-Tai^{a; *}

Affiliations: [a] Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China | [b] Positron Emission Tomography (PET) Center, Huashan Hospital, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Prof. Jin-tai Yu, MD, PhD, Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China. Tel.: +86 21 52888163; Fax: +86 21 62483421; E-mail: jintai_yu@fudan.edu.cn.

Note: [1] These authors contributed equally to this work.

Abstract: Mutations in Presenilin-1 (PSEN1) have been found to be associated with very early onset Alzheimer’s disease (VEOAD). Here, we reported two patients with VEOAD caused by de novo PSEN1 mutations. A 33-year-old man with a de novo p.F177S mutation in PSEN1 presented with progressive decline in memory and daily function. A 37-year-old woman with a de novo PSEN1 p.L381V mutation presented with onset memory impairment, developed cerebellar syndrome, rigidity, and spastic paraparesis. The Amyloid/Tau/Neurodegeneration (ATN) biomarker profiles of both patients were A + T + (N)+. Our finding increases the genetic knowledge of VEOAD and extends the ethnic distribution of PSEN1 mutations.

Keywords: Mutation, PSEN1, sporadic cases, very early onset Alzheimer’s disease

DOI: 10.3233/JAD-215167

Journal: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 65-71, 2022