Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members.

摘要: Mutations in the progranulin gene (GRN) are an important cause of frontotemporal lobar degeneration (FTLD) with ubiquitin and TAR DNA-binding protein 43 (TDP43)-positive pathology. The clinical presentation associated GRN mutations is heterogeneous may include probable Alzheimer's disease. All identified thus far disease through a uniform mechanism, i.e. loss functional or haploinsufficiency. To determine if expression plasma could predict mutation status be used as biological marker, we optimized ELISA studied samples consecutive FTLD series 219 patients, 70 control individuals, 72 early-onset patients nine symptomatic 18 asymptomatic relatives families. loss-of-function showed significantly reduced levels to about one third observed non-GRN carriers individuals (P < 0.001). No overlap distributions was between eight (range: 53-94 ng/ml) 191 115-386 ng/ml). Similar low were carriers. Importantly, analyses also patient (1.4%) carrying GRN. Biochemical further that only detects full-length GRN, no intermediate granulin fragments. This study demonstrates using plasma, pathogenic can accurately detected approximately 75% reduction suggests unbalanced metabolism whereby more processed into granulins. We propose reliable inexpensive tool identify all dementia populations at-risk individuals.