Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Feb 2017
Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases.
Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer's disease (AD) and Parkinson's disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap between FTD, AD and PD to assess shared pathobiology and identify novel genetic variants associated with increased risk for FTD. ⋯ Our findings demonstrate genetic pleiotropy in these neurodegenerative diseases and indicate that sporadic FTD is a polygenic disorder where multiple pleiotropic loci with small effects contribute to increased disease risk.
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J. Neurol. Neurosurg. Psychiatr. · Feb 2017
Defining SOD1 ALS natural history to guide therapeutic clinical trial design.
Understanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population. ⋯ SOD1A4V is an aggressive, but relatively homogeneous form of ALS. These SOD1-specific ALS natural history data will be important for the design and implementation of clinical trials in the ALSSOD1 patient population.
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J. Neurol. Neurosurg. Psychiatr. · Feb 2017
Association between naturally occurring anti-amyloid β autoantibodies and medial temporal lobe atrophy in Alzheimer's disease.
Naturally occurring autoantibodies against amyloid β (Aβ) peptide exist in the serum and cerebrospinal fluid (CSF) of healthy individuals. Recently, it was reported that administration of intravenous immunoglobulin at the mild cognitive impairment (MCI) stage of Alzheimer's disease (AD) reduces brain atrophy. ⋯ These results indicate that CSF levels of naturally occurring anti-Aβ autoantibodies are inversely associated with the degree of the VOI atrophy in patients with AD. Although the mechanism is unclear, CSF levels of naturally occurring anti-Aβ autoantibodies may be implicated in the progression of atrophy of the whole hippocampus, entorhinal cortex and amygdala, in AD.
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J. Neurol. Neurosurg. Psychiatr. · Feb 2017
Concomitant AD pathology affects clinical manifestation and survival in dementia with Lewy bodies.
To investigate whether concomitant Alzheimer's disease (AD) pathology, reflected by cerebrospinal fluid (CSF) biomarkers, has an impact on dementia with Lewy bodies (DLB) in terms of clinical presentation, cognitive decline, nursing home admittance and survival. ⋯ DLB-patients with a CSF AD profile have a more severe manifestation of the disease and a higher risk of institutionalisation and mortality. In clinical practice, CSF biomarkers may aid in predicting prognosis in DLB. In addition, DLB-patients with positive AD biomarkers could benefit from future treatment targeting AD pathology.