Ant pyramidal signs have been observed. Impairment of cerebellar function and multifocal cognitive loss was noticed by neurologic examination. Behavioral abnormalities with delusions, Recombinant?Proteins Kappa-Casein Protein visual hallucinations, confabulations, mental confusion were evident within the following days. These symptoms had been scarcely responsive to Quetiapine but had been partially controlled by the usage of Haloperidol. Neuropsychological assessment showed behavioral disturbances with depression and visual hallucinations, moderate-to-severe cognitive dysfunctions, mostly consisting of impairment of thought content material and semantic fluency, poor orientation in time and location, memory deficits, confabulation, dyspraxia. Laboratory analysis revealed raise of FT4 (9.9 ng/ dL, n.v. 0,70-1,48) and low TSH levels (0.13 UI/mL, n.v. 0,45-3,50). The imbalance of thyroid function was corrected by the adjustment of pharmacologic therapy for hyperthyroidism with transient optimistic effects on psychic disturbances (regression of delusions/hallucinations and improvement of mental confusion). CSF analysis showed absence of 14-3 protein. CSF levels of total tau protein had been 392 pg/ml (n.v. 500 pg/ml). EEG showed a diffuse slowing on the background activitytowards the delta rhythm. An improvement with the EEG profile was observed soon after neuroleptic treatment and correction of thyroid dysfunction. Brain MRI showed several small ischemic foci in white matter of both brain hemispheres, and diffuse cortical atrophy involving primarily left frontal and temporal lobi (Fig. three, panels b,e). All these clinical investigations were performed 2 years immediately after the illness onset. As a consequence of the prominence of behavioral modifications in her clinical picture and to brain MRI findings, the patient was initially diagnosed as frontotemporal dementia (FTD). Over the following months, the clinical picture evolved towards tetraparesis, extreme ataxia, and further cognitive deterioration. When the household history on the patient emerged and also the presence of a PRNP mutation was confirmed in her sister (Case 1), the analysis of PRNP gene was carried out also within this patient and revealed the presence from the Valine-to-Isoleucine substitution at codon 189 with Methionine/Valine polymorphism at codon 129. The patient died nine months following hospital discharge, about 33 months right after the onset of the disease. No autopsy was performed. Having said that, RT-QuIC evaluation of CSF sample collected in vitam was carried out and was good, confirming the presence of pathological prion protein. Taking into account her clinical findings, Case two met the WHO 1998 criteria or the updated criteria by Zerr et al. [51] for `possible’ sCJD, as she had no constructive ancillary tests. Nonetheless, the outcomes in the RT-QuIC test on CSF, created reasonable a diagnosis of `probable’ CJD in line with the proposed new criteria from the UK and Germany that permit any neurological LDLR Protein C-6His syndrome with a optimistic RT-QuIC.Di Fede et al. Acta Neuropathologica Communications(2019) 7:Page 7 ofCaseThis patient was a 71-year-old man using a 2-month history of short-term memory deficits and fluctuating confusion (Table 1). The family members history was unremarkable except for two circumstances of late-onset depression ( 60 years) in two sisters of his father. The patient underwent neurologic evaluation that resulted to become typical: a presumptive diagnosis of reactive depression was created along with a therapy with sertraline was recommended. Because the lack of response plus the worsening of cognitive symptoms, the patient was subje.