Serum progranulin levels in patients with frontotemporal lobar degeneration and Alzheimer's disease: detection of GRN mutations in a Spanish cohort.

Abstract

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.

• Authors: Anna Antonell, Silvia Gil, Raquel Sánchez-Valle, Mircea Balasa, Beatriz Bosch, Ma Carmen Prat, Anne-Cécile Chiollaz, Manel Fernández, Jordi Yagüe, José Luis Molinuevo, Albert Lladó
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 31 Issue 3 Pg. 581-91 ( 2012) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 22647257 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• GRN protein, human
• Intercellular Signaling Peptides and Proteins
• Progranulins

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (blood, epidemiology, genetics)
• Biomarkers (blood)
• Cohort Studies
• Female
• Frontotemporal Lobar Degeneration (blood, epidemiology, genetics)
• Humans
• Intercellular Signaling Peptides and Proteins (blood, genetics)
• Male
• Middle Aged
• Mutation (genetics)
• Progranulins
• Spain (epidemiology)