Among 124 876 cases and controls, genome-wide conjunction analyses of ALS, FTD, PD, AD, CBD, and PSP revealed significant genetic overlap between ALS and FTD at known ALS loci: rs13302855 and rs3849942 (nearest gene, C9orf72; P = .03 for rs13302855 and P = .005 for rs3849942) and rs4239633 (nearest gene, UNC13A; P = .03).
We propose that aggregation of ubiquitinated proteins into compact inclusions in PSP might be due to inhibition of the degradation of multiubiquitinated proteins by ubiquitin chains containing proximal UBB+1 rather than normal ubiquitin.
Despite UBB+1 polyubiquitination (an indication of proteasome inhibition), we demonstrate that UBB+1 and HSP40/HSP70 immunoreactivity do not co-localize in the pons of patients with PSP.
Here, we report that protein levels of the Rho-associated protein kinases (ROCK1 and ROCK2), p70 S6 kinase (S6K), and mammalian target of rapamycin (mTOR) were increased in PSP and CBD brains.
We performed CBI assessments with neuronavigation before and after high frequency cerebellar rTMS or sham TMS in two patients with PSP, using a double cone coil for the conditioning pulse and a figure-of-eight coil for the test pulse and treatments.
Our study suggests that the TRIM11 locus is a genetic modifier of PSP phenotype and potentially adds further evidence for the UPS having a key role in tau pathology, therefore representing a target for disease-modifying therapies.Ann Neurol 2018;84:485-496.
A significant association was observed for the TREM2p.R47H substitution in susceptibility to frontotemporal dementia (OR = 5.06; p-value = 0.001) and Parkinson's disease (OR = 2.67; p-value = 0.026), while no evidence of association with risk of amyotrophic lateral sclerosis, progressive supranuclear palsy or ischemic stroke was observed.
[<sup>18</sup>F]-THK5351 PET was performed in 34 patients: six with Parkinson's disease (PD), nine with multiple system atrophy with predominant parkinsonism (MSA-P), six with MSA with predominant cerebellar ataxia (MSA-C), and 13 with progressive supranuclear palsy (PSP) Richardson's syndrome.
Data obtained from 10 patients with clinical diagnosis MSA-P, 14 patients with CBS and 21 patients with PSP, which were analyzed using Tukey honest significant difference post-hoc test, revealed significant differences of perfusion P < .05 between MSA-P and PSP within the cerebellum and thalamus.
When compared with HC, MSA and PSP patients shared the changes in PD, with a few exceptions: in MSA, Lachnospiraceae were not lower, and Prevotellaceae were reduced; in PSP, Lactobacillaceae were similar, and Streptococcaceae were reduced.
In this study we used in situ hybridization to detect the common deletion in sections of midbrain from patients with PD, multiple system atrophy-parkinsonian type (MSA-P), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), age-matched controls, and individuals of different ages.
The Magnetic Resonance Parkinsonism Index (MRPI) utilizes linear and surface (planimetry) measurements and has been proposed as a dual MRI biomarker, with high values indicative of PSP and low values of MSA.
Multimodal MRI improved the detection of disease-specific neurodegenerative patterns in PSP and MSA-P and highlights its potential to improve the diagnostic accuracy of atypical parkinsonian disorders.
Twenty-five patients with Progressive Supranuclear Palsy - Richardson's Syndrome (PSP-RS), nine with cerebellar and nine with parkinsonian Multiple System Atrophy variants (MSA-C and MSA-P), forty-seven with Parkinson's Disease (PD) and twenty-seven HC underwent a 1.5 T brain-MR protocol including high-resolution 3D T1-weighted and 25-direction diffusion tensor imaging sequences.
The VOI analysis based on spatially normalized PRESTO images may be useful for depicting hypointensity, indicative of abnormal iron depositions, of the putamen and red nucleus in the diagnosis of MSA-P and PSP.
<sup>123</sup>I-FP-CIT SPECT was performed at a single-center level on 370 individuals with PS, including 280 patients with Parkinson's disease (PD), 21 with multiple system atrophy-parkinsonian type (MSA-P), 41 with progressive supranuclear palsy (PSP) and 28 with corticobasal syndrome (CBS) (mean age 70.3 years, 47% female, mean disease duration at scan 1.4 year), as well as 208 age- and gender-matched control subjects.
We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge.