A novel presenilin1 mutation (Q223R) associated with early onset Alzheimer's disease, dysarthria and spastic paraparesis and decreased Abeta levels in CSF.
OBJECTIVE
A novel presenilin1 (PSEN1) mutation associated with dementia and spastic paraplegia in a family with five affected individuals is described. The index patient was a 35-year-old man presenting with cognitive decline, behavioural symptoms, dysarthria, and gait disorder due to spasticity.


RESULTS
Genetic analysis revealed a missense mutation Gln223Arg in exon 7. Initial CSF analysis revealed drastically decreased Abeta42 level despite marginally decreased FDG metabolism.


CONCLUSIONS
Cerebrospinal fluid biomarker analysis might point towards genetic analysis of PSEN1 in patients with positive family history and age of onset below 60 years.
Uttner
I
I
Department of Neurology, University Hospital, Ulm, Germany.
Kirchheiner
J
J
Tumani
H
H
Mottaghy
F M
FM
Lebedeva
E
E
Ozer
E
E
Ludolph
A C
AC
Huber
R
R
von Arnim
C A F
CA
D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D004401:Dysarthria / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D005190:Family; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D020336:Paraparesis, Spastic / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D049268:Positron-Emission Tomography; D053764:Presenilin-1 / Q000235:genetics*
D016229:Amyloid beta-Peptides; D053764:Presenilin-1; D019788:Fluorodeoxyglucose F18