CSF Studies Facilitate DNA Diagnosis in Familial Alzheimer's Disease Due to a Presenilin-1 Mutation

Article type: Short Communication

Authors: de Bot, Susanne T.^{a; *} | Kremer, H.P.H.^a | Dooijes, Dennis^c | Verbeek, Marcel M.^{a; b}

Affiliations: [a] Department of Neurology, Donders Centre for Brain Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands | [b] Laboratory of Pediatrics and Neurology, Alzheimer Centre Nijmegen, Nijmegen, The Netherlands | [c] Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands

Correspondence: [*] Corresponding author: Susanne T. de Bot, MD, Department of Neurology, Radboud University Nijmegen Medical Centre, PO box 9101, 6500 HB, Nijmegen, The Netherlands. Tel.: +31 24 3618860; Fax: +31 24 3541122; E-mail: ST.Bot@neuro.umcn.nl.

Abstract: In sporadic Alzheimer's disease (AD), cerebrospinal fluid (CSF) analysis is becoming increasingly relevant to establish an early diagnosis. We present a case of familial AD due to a presenilin-1 mutation in which CSF studies suggested appropriate DNA diagnostics. A 38 year old Dutch man presented with dementia, spastic paraparesis, and frontal executive function impairments, mimicking familial Creutzfeldt Jakob disease and frontotemporal dementia. CSF studies, revealing increased total tau and phosphorylated-tau levels with decreased amyloid-β42, distinguished familial AD from Creutzfeldt Jakob disease and frontotemporal dementia. A causative p.L424R PSEN1 mutation was subsequently identified.

Keywords: Amyloid-β₄₂, cerebrospinal fluid biomarkers, familial Alzheimer's disease, phosphorylated-tau, p.L424R, presenilin-1 mutation, tau protein

DOI: 10.3233/JAD-2009-1038

Journal: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 53-57, 2009