title: Progranulin plasma levels as potential biomarker for the identification of GRN deletion carriers. A case with atypical onset as clinical amnestic Mild Cognitive Impairment converted to Alzheimer's disease.
abstract: Progranulin (GRN) mutations are associated with different clinical phenotypes, including Frontotemporal Lobar Degeneration (FTLD), Corticobasal Degeneration and Alzheimer's disease (AD). In addition, the range of age at onset is very wide and patients presenting initial symptoms around eighty years have been described. Previous studies demonstrated that progranulin plasma levels determination may be a reliable method to identify GRN deletion carriers. We thus evaluated progranulin plasma levels in all patients followed at our Alzheimer's Centre whose plasma was available (n=176) and found four patients displaying low values. Three of them carried the CACT deletion in exon 7 and their clinical diagnosis was behavioral variant Frontotemporal Dementia. We also identified a patient carrying a previously reported CAGT deletion in exon 5. Here, we report on this case. The onset of symptoms was at 77 years and the initial diagnosis was of amnestic Mild Cognitive Impairment (aMCI), which converted to AD six months later. In the following years, the patient also developed behavioral disturbances, gait apraxia and parkinsonian symptoms. At present, she is 84 years old and is still followed-up periodically. This case confirms progranulin plasma levels as a reliable biomarker to identify GRN deletion carriers and discriminate between FTLD and other dementias which may mimic it. We thus encourage the inclusion of this non-invasive and easy test in clinical practice.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Centre, IRCCS Fondazione Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. mcarecchio@gmail.com
authors.forename: Miryam
authors.initials: M
authors.lastname: Carecchio
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Milena
authors.initials: M
authors.lastname: De Riz
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guidi
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Comi
authors.forename: Francesca
authors.initials: F
authors.lastname: Cortini
authors.forename: Eliana
authors.initials: E
authors.lastname: Venturelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Restelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Francesco
authors.initials: F
authors.lastname: Monaco
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D020233:Gait Disorders, Neurologic / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D006580:Genetic Carrier Screening / Q000379:methods*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics*; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D000077153:Progranulins; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C492314:GRN protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins