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- Hampel, H., et al.
(author)
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State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer's disease
- 2022
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 159-177
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Journal article (peer-reviewed)abstract
- Recent advances in developing disease-modifying therapies (DMT) for Alzheimer's disease (AD), and the recognition that AD pathophysiology emerges decades before clinical symptoms, necessitate a paradigm shift of health-care systems toward biomarker-guided early detection, diagnosis, and therapeutic decision-making. Appropriate incorporation of cerebrospinal fluid biomarker analysis in clinical practice is an essential step toward system readiness for accommodating the demand of AD diagnosis and proper use of DMTs-once they become available. However, the use of lumbar puncture (LP) in individuals with suspected neurodegenerative diseases such as AD is inconsistent, and the perception of its utility and safety differs considerably among medical specialties as well as among regions and countries. This review describes the state-of-the-art evidence concerning the safety profile of LP in older adults, discusses the risk factors for LP-associated adverse events, and provides recommendations and an outlook for optimized use and global implementation of LP in individuals with suspected AD.
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- Hampel, H., et al.
(author)
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The use of lumbar puncture and safety recommendations in Alzheimer's disease: a plain language summary
- 2022
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In: Neurodegenerative Disease Management. - : Future Medicine Ltd. - 1758-2024 .- 1758-2032. ; 12:5
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Journal article (peer-reviewed)abstract
- What is this summary about? This is a plain language summary of an article published in Alzheimer's & Dementia. It looks at a type of test called a lumbar puncture (also known as spinal tap) used in people suspected of having Alzheimer's disease or some other form of dementia. This summary focuses on how to do a lumbar puncture safely. Why is this important? Alzheimer's disease is a progressive condition, which means it gets worse over time. This leads to difficulties with thinking and memory. People with Alzheimer's disease show a build up of proteins called amyloid-beta and tau in the brain. This is followed by a gradual loss of brain cells and brain function. The changes in the brain are thought to occur years before symptoms appear. Lumbar puncture is a medical procedure during which samples of cerebrospinal fluid are collected. In Alzheimer's disease, it is used to examine cerebrospinal fluid biomarkers that can help diagnose disease. Lumbar puncture is traditionally considered as a painful and invasive procedure with frequent side effects. However, multiple studies indicate that a lumbar puncture can be performed safely. Side effects are typically mild and do not require specialist intervention. What are the key takeaways? Despite the low risk of serious complications associated with a lumbar puncture, physicians and their patients may be reluctant to recommend or undergo this procedure. Patient education, specialist training, as well as new methods concerning patient safety are important factors to support the widespread use of lumbar puncture in Alzheimer's disease.
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- Scussolini, Paolo, et al.
(author)
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Global River Discharge and Floods in the Warmer Climate of the Last Interglacial
- 2020
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 47:18
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Journal article (peer-reviewed)abstract
- We investigate hydrology during a past climate slightly warmer than the present: the last interglacial (LIG). With daily output of preindustrial and LIG simulations from eight new climate models we force hydrological model PCR-GLOBWB and in turn hydrodynamic model CaMa-Flood. Compared to preindustrial, annual mean LIG runoff, discharge, and 100-yr flood volume are considerably larger in the Northern Hemisphere, by 14%, 25%, and 82%, respectively. Anomalies are negative in the Southern Hemisphere. In some boreal regions, LIG runoff and discharge are lower despite higher precipitation, due to the higher temperatures and evaporation. LIG discharge is much higher for the Niger, Congo, Nile, Ganges, Irrawaddy, and Pearl and lower for the Mississippi, Saint Lawrence, Amazon, Parana, Orange, Zambesi, Danube, and Ob. Discharge is seasonally postponed in tropical rivers affected by monsoon changes. Results agree with published proxies on the sign of discharge anomaly in 15 of 23 sites where comparison is possible.
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- Prudencio, Mercedes, et al.
(author)
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Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3
- 2020
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:566
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Journal article (peer-reviewed)abstract
- Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.
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