Title:Novel PSEN1 (P284S) Mutation Causes Alzheimer's Disease with Cerebellar
Amyloid β-Protein Deposition
Volume: 19
Issue: 7
Author(s): Mingrong Xia, Chenhao Gao, Huayuan Wang, Junkui Shang, Ruijie Liu, Yang You, Weizhou Zang*Jiewen Zhang*
Affiliation:
- Department of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou
450003, Henan, China
- Department of Neurology, Henan University People’s Hospital, Henan Provincial People’s
Hospital, Zhengzhou 450003, Henan, China
- Department of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou
450003, Henan, China
- Department of Neurology, Henan University People’s Hospital, Henan Provincial People’s
Hospital, Zhengzhou 450003, Henan, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450003,
Henan, China
Keywords:
Alzheimer's disease, PSEN1, P284S mutation, 18F-florbetapir (AV-45) PET, cerebellar Aβ deposition, cerebral cortex.
Abstract:
Background/Objective: AD-associated PSEN1 mutations exhibit high clinical heterogeneity.
The discovery of these mutations and the analysis of their associations with cases such as EOAD should
be critical to understanding AD's pathogenesis.
Methods: We performed clinical analysis, neuroimaging, target region capture and high-throughput sequencing,
and Sanger sequencing in a family of 3 generations. The underlying Alzheimer’s pathology
was evaluated using biomarker evidence obtained from cerebrospinal fluid (CSF) amyloid testing and
18F-florbetapir (AV-45) PET imaging.
Results: Target region capture sequencing revealed a novel heterozygous C to T missense point mutation
at the base position 284 (c.850 C>T) located in exon 8 of the PSEN1 gene, resulting in a Prolineto-
Serine substitution (P284S) at codon position 850. The mutation was also identified by Sanger sequencing
in 2 family members, including proband and her daughter and was absent in the other 4 unaffected
family members and 50 control subjects. Cerebrospinal fluid (CSF) amyloid test exhibited biomarker
evidence of underlying Alzheimer’s pathology. 18F-florbetapir (AV-45) PET imaging indicated
extensive cerebral cortex and cerebellar Aβ deposition.
Conclusions: We discovered a novel PSEN1 pathogenic mutation, P284S, observed for the first time in
a Chinese family with early-onset AD.
