P-Tau as prognostic marker in long term follow up for patients with shunted iNPH.

Objective: Diagnosis of idiopathic Normal Pressure Hydrocephalus (iNPH) relies solely on clinical and radiological criteria while, unlike other neurological diseases, the analysis of cerebrospinal fluid markers is not used in clinical practice. Nevertheless, the overlapping of neurodegenerative diseases affects the long-term shunt efficacy and this occurrence should be detected before surgery. Therefore, we performed this study in order to assess the correlation between pre-surgical levels of CSF Beta Amyloid protein, Total Tau protein and Phospho-Tau protein with long-term clinical outcome. Methods: Between March 2012 and May 2016 we prospective evaluated all patients with iNPH according to guidelines criteria and we analysed CSF concentration of these proteins before and during surgery. Two years after surgery we evaluated iNPH score for all patients, grouping them in shunt responders and non-responders. Results: A total of 117 patients were included: Tap Test non-responders were 58 and at two years we had 35 shunt responders and 15 shunt non-responders. We found a significative difference between shunt-responders and shunt non-responders for pre surgical T-Tau (p: 0.02) and for P-Tau (p: 0.01). All the proteins were significantly associated with clinical outcome after surgery with different cut-off values; in particular, having a 'low' value of T-Tau, P-Tau and Aß1-42 resulted in favourable outcome after surgery. Conclusions: Low level of P-Tau is a useful CSF biochemical prognostic factor for good clinical outcome at least two years after shunt; meanwhile a lower Aß1-42 might suggest that the pathophysiology of iNPH could have something in common with other neurodegenerative diseases of the elderly.

Assessment of the Incremental Diagnostic Value of Florbetapir F 18 Imaging in Patients With Cognitive Impairment: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study.

IMPORTANCE: Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. OBJECTIVE: To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. RESULTS: Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). CONCLUSIONS AND RELEVANCE: Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

Gene expression profile in fibroblasts of Huntington's disease patients and controls.

Huntington's disease is an inherited disorder caused by expanded stretch of consecutive trinucleotides (cytosine-adenosine-guanine, CAG) within the first exon of the huntingtin (HTT) gene on chromosome 4 (p16.3). The mutated huntingtin (mHTT) gains toxic function, probably through mechanisms that involve aberrant interactions in several pathways, causing cytotoxicity. Pathophysiology of disease involves several tissues; indeed it has been shown that there is a broad toxic effect of mHTT in the peripheral tissue of patients with HD, not only in the central nervous system. In this study we compared gene expression profiles (GEP) of HD fibroblasts and matched controls using microarray technology. We used RT-PCR to test the consistency of the microarray data and we found four genes up-regulated in HD patients with respect to control individuals. The genes appear to be involved in different pathways that have been shown to be perturbed even in HD models and patients. Although our study is preliminary and has to be extended to a larger cohort of HD patients and controls, nevertheless it shows that gene expression profiles seem to be altered in the fibroblasts of HD patients. Validation of the differential expressions at the protein level is required to ascertain if this cell type can be considered a suitable model for the identification of HD biomarkers.