We studied the clinical and pathologic features of HpScl in 205 consecutive patients with dementia who came to autopsy from 1997 to 2008, focusing on associations with TAR DNA-binding protein 43 (TDP-43) pathology and allelic variants in the progranulin (GRN) and apolipoprotein E (APOE).
An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, resulting in the disease frontotemporal lobar dementia.
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.
Due to the functions of PGRN in neuronal survival and the clinicopathological overlaps between FTD and other dementias it is likely that reduced PGRN expression is associated with the progression of other neurodegenerative brain diseases including Alzheimer's disease.
Once a cure for GRN-related neurodegeneration becomes available, this biomarker will be an important tool in the effort to personalize treatment of dementia.
The GRN gene should be analyzed in patients with PCA, particularly when the damage progresses to anterior cerebral regions and a family history of dementia is present.
The discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases leading to dementia has brought renewed interest in progranulin and its functions in the central nervous system.
We describe a case of late onset frontotemporal dementia carrying the g.1977_1980 delCACT (Thr272fs) mutation in progranulin (GRN) gene, characterized by a positive family history for dementia and a clinical phenotype resembling dementia with Lewy bodies.
This is consistent with the finding that miR-659 binding to the high risk T allele of rs5848 may augment translational inhibition of GRN and alter risk of FTD and possibly other dementias.