The sample included in the study by Hollingworth et al 17 included 1120 individuals "diagnosed with late-onset probable AD [Alzheimer's disease]." Their results are higher than those from other NPI studies.
To determine if expression of GRN in plasma could predict GRN mutation status and could be used as a biological marker, we optimized a GRN ELISA and studied plasma samples of a consecutive clinical FTLD series of 219 patients, 70 control individuals, 72 early-onset probable Alzheimer's disease patients and nine symptomatic and 18 asymptomatic relatives of GRN mutation families.
In this study, using our GRN ELISA as a screening tool, we analysed 72 patients with clinically diagnosed early-onset probable Alzheimer's disease for mutations in GRN and identified one patient (1.4% of the population) carrying a loss-of-function mutation.
DNA and plasma samples of 72 early-onset probable Alzheimer's disease patients (mean age at onset ± SD: 57.9 ± 6.4 years; range: 37 65 years; 61% women) and 70 unrelated control individuals (mean age ± SD: 66.3 ± 11.0 years; range: 46 85 years; 50% women) were also ascertained at Mayo Jacksonville.
If a disease modifying treatment for either Alzheimer's disease or FTLD becomes available in the future, then, based on the finding above and knowing that that FTLD usually starts early, one could make the case that it would be reasonable to screen early-onset probable Alzheimer's disease cases with a plasma measure for GRN.
Two brain magnetic resonance imaging studies performed 8 months after illness onset indicated probable CJD, given lack of prior metabolic and anoxic insults.
The index patient presented at the Memory Clinic, University Hospitals Leuven, at the age of 50 years with a prior diagnosis of early onset clinically probable AD.
The neuropathologic changes of this transitional state are consistent with the density and distribution of the tau-associated neurofibrillary and abeta-associated amyloid features of very early Alzheimer's disease (Bennett et al., 2005) and present long before the clinical onset of probable Alzheimer's disease (Gomez-Isla et al., 1996).
Observational studies of the pre-cursor phase of solar flares have shown that there are many and varied signatures that may or may not indicate the probable onset of a flare.
The median ages at onset of the probable CJD and control patients were 60- (range: 33 76) and 58-year-old (range: 43 88), respectively.
