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We are grateful to the participants of this study for their cooperation. The authors are indebted to Teresa Botta-Orfila and Rosa Ma Alvarez for excellent technical assistance. This work was supported by grants to Dr Raquel Sanchez-Valle (FIS080036. ISCIII. Cofinancia FEDER. Union Europea. Otra manera de hacer Europa), to Dr Jose Luis Molinuevo (CSD2010-00045), and to Dr Albert Llado (PI11/00234. ISCIII. Cofinancia FEDER. Union Europea. Otra manera de hacer Europa).

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Serum Progranulin Levels in Patients with Frontotemporal Lobar Degeneration and Alzheimer's Disease: Detection of GRN Mutations in a Spanish Cohort

Publicat a:Journal Of Alzheimers Disease. 31 (3): 581-591 - 2012-01-01 31(3), DOI: 10.3233/JAD-2012-112120

Autors: Antonell, A; Gil, S; Sánchez-Valle, R; Balasa, M; Bosch, B; Chiollaz, AC; Fernández, M; Molinuevo, JL; Lladó, A; Prat, MC; Yagüe, J

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Progranulin gene (GRN) mutations cause frontotemporal lobar degeneration (FTLD) with TDP43-positive inclusions, although its clinical phenotype is heterogeneous and includes patients classified as behavioral variant-FTLD (bvFTLD), progressive non-fluent aphasia (PNFA), corticobasal syndrome, Alzheimer's disease (AD), or Parkinson's disease (PD). Our main objective was to study if low serum progranulin protein (PGRN) levels may detect GRN mutations in a Spanish cohort of patients with FTLD or AD. Serum PGRN levels were measured in 112 subjects: 17 bvFTLD, 20 PNFA, 4 semantic dementia, 34 sporadic AD, 9 AD-PSEN1 mutation carriers, 10 presymptomatic-PSEN1 mutation carriers, and 18 control individuals. We detected 5 patients with PGRN levels below 94 ng/mL: two of them had a clinical diagnosis of bvFTLD, two of PNFA, and one of AD. The screening for GRN mutations detected two probable pathogenic mutations (p.C366fsX1 and a new mutation: p.V279GfsX5) in three patients and one mutation of unclear pathogenic nature (p.C139R) in one patient. The other patient showed a normal GRN sequence but carried a PRNP gene mutation. We observed no differences in serum PGRN levels between controls (mean = 145.5 ng/mL, SD = 28.5) and the other neurodegenerative diseases, except for the carriers of pathological GRN gene mutations (mean = 50.5 ng/mL, SD = 21.2). Null GRN mutation carriers also showed lower serum PGRN levels than the patient who was a carrier of p.C139R (92.3 ng/mL) and the one who was a carrier of the PRNP mutation (76.9 ng/mL). In conclusion, we detected GRN null mutations in patients with severely reduced serum PGRN levels, but not in patients with slightly reduced PGRN levels.

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