Sleep and longitudinal cognitive performance in preclinical and early symptomatic Alzheimer ’s disease
In this study, we hypothesized that longitudinal changes in cognitive function will have a non-linear relationship with total sleep time, time spent in non-REM and REM sleep, sleep efficiency and non-REM slow wave activity.To test this hypothesis, we monitored sleep-wake activity over 4–6 nights in 100 participants who underwent standardized cognitive testing longitudinally,APOE genotyping, and measurement of Alzheimer ’s disease biomarkers, total tau and amyloid-β42 in the CSF. To assess cognitive function, individuals completed a neuropsychological testing battery at each clinical visit that included the Free and Cu...
Source: Brain - October 20, 2021 Category: Neurology Source Type: research
Whole-exome sequencing reveals a role of HTRA1 and EGFL8 in brain white matter hyperintensities
AbstractWhite matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on their volume, the contribution of rare variants to the WMH burden in the general population remains largely unexplored. We conducted a comprehensive analysis of this burden in the UK Biobank using publicly available whole-exome sequencing data (n up to 17 830) and found a splice-site variant inGBE1, encoding 1,4-alpha-glucan branching enzyme 1, to be a...
Source: Brain - October 9, 2021 Category: Neurology Source Type: research
MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase
AbstractStriated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants inMLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable su...
Source: Brain - September 28, 2021 Category: Neurology Source Type: research
Another step towards defining the genetic landscape of rhabdomyolysis
This scientific commentary refers to ‘MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline high serum creatine kinase’, by Lopes Abath Netoet al. (doi:10.1093/brain/awab275). (Source: Brain)
Source: Brain - September 28, 2021 Category: Neurology Source Type: research
A passive and objective measure of recognition memory in Alzheimer ’s disease using Fastball memory assessment
We present Fastball, a new EEG method for the passive and objective measurement of recognition memory, that requires no behavioural memory response or comprehension of the task . Younger adults, older adults and Alzheimer’s disease patients (n = 20 per group) completed the Fastball task, lasting just under 3 min. Participants passively viewed rapidly presented images and EEG assessed their automatic ability to differentiate between images based on previous exposure, i.e. old/new. Participants were not instructed to attend to previous ly seen images and provided no behavioural response. Following the Fastball task, pa...
Source: Brain - September 20, 2021 Category: Neurology Source Type: research
Proust and his neurologists: the challenge of functional disorders
Functional neurological disorders are a major challenge. For clinicians and patients alike, they are one of the most difficult conditions to deal with, not least because treatment options seem so limited. Modern clinicians feel impotent when confronted by them. There is simply no easy fix. Patients often have no effective intervention. When an ‘organic’ diagnosis cannot be made, they are frequently left isolated, perplexed—and symptomatic. But, of course, functional disorders are not new. They have always been present. Perhaps one of the most celebrated—and complex—of sufferers was Marcel Proust. One hundred and ...
Source: Brain - September 3, 2021 Category: Neurology Source Type: research
Erratum to: Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
Manuela Wiessner, Reza Maroofian, Meng-Yuan Ni, Andrea Pedroni, Juliane S. M üller, Rolf Stucka, Christian Beetz, Stephanie Efthymiou, Filippo M. Santorelli, Ahmed A. Alfares, Changlian Zhu, Anna Uhrova Meszarosova, Elham Alehabib, Somayeh Bakhtiari, Andreas R. Janecke, Maria Gabriela Otero, Jin Yun Helen Chen, James T. Peterson, Tim M. Strom, Peter De Jonghe, Tine Deconinc k, Willem De Ridder, Jonathan De Winter, Rossella Pasquariello, Ivana Ricca, Majid Alfadhel, Bart P. van de Warrenburg, Ruben Portier, Carsten Bergmann, Saghar Ghasemi Firouzabadi, Sheng Chih Jin, Kaya Bilguvar, Sherifa Hamed, Mohammed Abdelhameed, Nou...
Source: Brain - August 31, 2021 Category: Neurology Source Type: research
Erratum to: The GGC repeat expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy type 3
Jiaxi Yu, Jianwen Deng, Xueyu Guo, Jingli Shan, Xinghua Luan, Li Cao, Juan Zhao, Meng Yu, Wei Zhang, He Lv, Zhiying Xie, LingChao Meng, Yiming Zheng, Yawen Zhao, Qiang Gang, Qingqing Wang, Jing Liu, Min Zhu, Binbin Zhou, Pidong Li, Yinzhe Liu, Yang Wang, Chuanzhu Yan, Daojun Hong, Yun Yuan, Zhaoxia Wang. The GGC repeat expansion inNOTCH2NLC is associated with oculopharyngodistal myopathy type 3.Brain. 2021;144(6):1819-1832. doi:10.1093/brain/awab077 (Source: Brain)
Source: Brain - August 26, 2021 Category: Neurology Source Type: research
Amyloid- β toxicity modulates tau phosphorylation through the PAX6 signalling pathway
In conclusion, we show that signalling pathways that include CDK/pRB/E2F1 modulate neuronal death signals by activating downstream transcription facto rs c-Myb and PAX6, leading to GSK-3β activation and tau pathology, providing novel potential targets for pharmaceutical intervention. (Source: Brain)
Source: Brain - August 24, 2021 Category: Neurology Source Type: research
BMP receptor blockade overcomes extrinsic inhibition of remyelination and restores neurovascular homeostasis
AbstractExtrinsic inhibitors at sites of blood –brain barrier disruption and neurovascular damage contribute to remyelination failure in neurological diseases. However, therapies to overcome the extrinsic inhibition of remyelination are not widely available and the dynamics of glial progenitor niche remodelling at sites of neurovascular dysfun ction are largely unknown. By integratingin vivo two-photon imaging co-registered with electron microscopy and transcriptomics in chronic neuroinflammatory lesions, we found that oligodendrocyte precursor cells clustered perivascularly at sites of limited remyelination with deposit...
Source: Brain - August 24, 2021 Category: Neurology Source Type: research
Towards a comprehensive 3D mapping of tau progression in early Alzheimer ’s disease
This scientific commentary refers to ‘Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe’, by Yushkevichet al. (doi:10.1093/brain/awab262). (Source: Brain)
Source: Brain - August 23, 2021 Category: Neurology Source Type: research
Biallelic PI4KA variants cause a novel neurodevelopmental syndrome with hypomyelinating leukodystrophy
In conclusion, we report a novel severe metabolic disorder caused byPI4KA malfunction, highlighting the importance of phosphoinositide signalling in human brain development and the myelin sheath. (Source: Brain)
Source: Brain - August 20, 2021 Category: Neurology Source Type: research
Reply: Functional cognitive disorder: dementia ’s blind spot
National Institute for Health Research10.13039/501100000272NIHR Academic Clinical FellowshipAlzheimer's Research UK& RosetreesNational Institute for Health Research Sheffield Biomedical Research CentreNIHR10.13039/100006662Medical Research Council10.13039/501100000265Wellcome Trust& the Royal SocietyWellcome Clinical Research Career Development FellowshipNational Institute for Health Research University College London Hospitals Biomedical Research CentreNIHR Clinician Scientist AwardInnovative Medicines Initiative10.13039/501100010767David Telling Charitable TrustNational Research Scotland Career Researcher Fellowship (Source: Brain)
Source: Brain - August 16, 2021 Category: Neurology Source Type: research
Autoantibodies and microglia: boon or bane?
This scientific commentary refers to ‘MOG autoantibodies trigger a tightly controlled FcR and BTK-driven microglia proliferative response’ by Pellerinet al. (doi:10.1093/brain/awab231). (Source: Brain)
Source: Brain - August 13, 2021 Category: Neurology Source Type: research
Dying-back of ascending noradrenergic projections in Parkinson ’s disease
This scientific commentary refers to ‘Regional locus coeruleus degeneration is uncoupled from noradrenergic terminal loss in Parkinson’s disease’, by Doppleret al. (doi:10.1093/brain/awab236). (Source: Brain)
Source: Brain - August 11, 2021 Category: Neurology Source Type: research
