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P2‐204: Phenotypic Variability in C9ORF72 Mutation Carriers from the German FTLD‐Consortium
Author(s) -
Diehl-Schmid Janine,
Straub Sarah,
Müller-Sarnowski Felix,
Grimmer Timo,
Otto Markus
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1372
Subject(s) - c9orf72 , frontotemporal dementia , amyotrophic lateral sclerosis , dementia , medicine , psychiatry , family history , disease , depression (economics) , trinucleotide repeat expansion , mutation , psychology , genetics , biology , allele , gene , economics , macroeconomics
onset, 75.0 [63-77] years) and 12 (non-carrier) family members followed at the Knight Alzheimer Disease Research Center (1985-2015), and 1115 individuals with autopsy-confirmed LOAD (median age-at-onset, 74.0 [60-101] years) from the National Alzheimer Coordinating Center database (09/2005-12/ 14). Results: Seven (70%) mutation carriers developed AD dementia. No differences were observed between mutation carriers and individuals with LOAD concerning age-atsymptomatic onset, presenting symptoms, duration, or rate of progression of dementia. Comorbid psychosis was observed in 71% of mutation carriers, but in only 24% of individuals with LOAD (p1⁄4.01). The distribution of Alzheimer disease neuropathologic change in PSEN1 A79V mutation carriers was similar to that previously reported in LOAD. Conclusions: In this family, the amyloidogenic PSEN1 A79Vmutation recapitulated the clinical attributes of LOAD. Previously reported clinical phenotypic differences between individuals with ADAD and LOAD may reflect ageor mutation-dependent effects. This finding has important implications for the extension of results from studies with individuals with ADAD to LOAD, including therapeutic trials.