Mingrong Xia, Chenhao Gao, Huayuan Wang, Junkui Shang, Ruijie Liu, Yang You, Weizhou Zang* and Jiewen Zhang* Pages 523 - 529 ( 7 )
<p>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. <p> 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 <sup>18</sup>F-florbetapir (AV-45) PET imaging. <p> 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. <sup>18</sup>F-florbetapir (AV-45) PET imaging indicated extensive cerebral cortex and cerebellar Aβ deposition. <p> Conclusions: We discovered a novel PSEN1 pathogenic mutation, P284S, observed for the first time in a Chinese family with early-onset AD.</p>
Alzheimer's disease, PSEN1, P284S mutation, <sup>18</sup>F-florbetapir (AV-45) PET, cerebellar Aβ deposition, cerebral cortex.