We investigated whether progranulin plasma levels are predictors of the presence of progranulin gene (GRN) null mutations or of the development of symptoms in asymptomatic at risk members participating in the Genetic Frontotemporal Dementia Initiative, including 19 patients, 64 asymptomatic carriers, and 77 noncarriers.
Although CSF sTREM2 levels are not raised in FTD overall or in a particular clinical subtype of FTD, levels are raised in familial FTD associated with GRN mutations and in FTD syndromes due to AD pathology.
One hundred and sixty-seven mutation carriers (75 GRN, 60 C9orf72, and 32 MAPT) were included from the Genetic FTD Initiative (GENFI) study, a large international cohort of genetic FTD.
In FTD, the granulin (GRN) gene has the highest number of different mutations (79/231 = 34%) and the second highest number of associated FTD families after C9orf72.
In sum, CSF-Neurofilament light chain and CSF-Progranulin seem to be promising biomarkers for FTD, the latter predominantly for assumed TDP43-mediated FTD.
Cognitively intact first-degree relatives of symptomatic GRN+ FTD patients with identified <i>GRN</i> mutations (pGRN+; <i>N</i> = 11, mean age = 41.4) and matched yCTL (<i>N</i> = 11, mean age = 53.6) were identified.
Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16.
Patients with GRN mutations present with a uniform subtype of TAR DNA-binding protein 43 (TDP-43) pathology at autopsy (FTLD-TDP type A); however, age at onset and clinical presentation are variable, even within families.
Five GRN mutation carriers free offrontotemporal dementia (FTD) and 11 non-carriers from families with FTD-GRN underwent functional MRI while solving matrix-reasoning problems.
FTD usually belongs to the frontotemporal lobar degeneration (FTLD) disease group, and its familial forms are dominantly inherited and linked to a group of genes relevant to frontal and temporal brain pathology, such as MAPT, GRN, C9ORF72, TARDBP, CHMP2B, VCP, and FUS.
We in6/2/2018vestigated hippocampal subfield volumes in a cohort of 75 patients with genetic FTD (age: mean (standard deviation) 59.3 (7.7) years; disease duration: 5.1 (3.4) years; 29 with MAPT, 28 with C9orf72, and 18 with GRN mutations) compared with 97 age-matched controls (age: 62.1 (11.1) years).
PurposeTo define the genetic spectrum and relative gene frequencies underlying clinical frontotemporal dementia (FTD).MethodsWe investigated the frequencies and mutations in neurodegenerative disease genes in 121 consecutive FTD subjects using an unbiased, combined sequencing approach, complemented by cerebrospinal fluid Aβ<sub>1-42</sub> and serum progranulin measurements.
Our results indicate that central nervous progranulin reduction is not restricted to the relatively rare cases of FTD caused by GRN LoF mutations, but also contributes to the more common GRN-negative forms of FTD.