Alzheimer's disease (AD) is a neurodegenerative brain disorder that has an increasingly large burden on health and social care systems. The pathophysiology involves the accumulation of extracellular amyloid-beta plaques (Aβ) and intracellular neurofibrillary tangles contributing to neuronal death and leading to cognition impairment. However, its cause remains poorly understood, and there is no cure for AD despite extensive research and billions of dollars spent over decades. Currently, there are only four US Food and Drug Administration (FDA) approved drugs and one combination therapy available in the market for the symptomatic relief of AD. Since 2003, no new drug has been approved by the FDA for the treatment of AD. Researchers continue to explore new treatments and therapeutic strategies to treat AD. The need for novel discoveries on therapeutic targets and the development of new therapeutic approaches is imminent when considering the current expectations regarding the increased number of AD cases each year and the huge financial cost amounted to healthcare. This review focused on the current status of drugs in the clinical pipeline targeting β-amyloid, tau phosphorylation, or neurotransmitter dysfunction for therapeutic control of Alzheimer's disease.
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http://dx.doi.org/10.1016/j.cct.2021.106549 | DOI Listing |
Ann Neurol
January 2025
Research Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.
Objective: Despite diagnostic criteria refinements, Parkinson's disease (PD) clinical diagnosis still suffers from a not satisfying accuracy, with the post-mortem examination as the gold standard for diagnosis. Seminal clinicopathological series highlighted that a relevant number of patients alive-diagnosed with idiopathic PD have an alternative post-mortem diagnosis. We evaluated the diagnostic accuracy of PD comparing the in-vivo clinical diagnosis with the post-mortem diagnosis performed through the pathological examination in 2 groups.
View Article and Find Full Text PDFJ Imaging Inform Med
January 2025
Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland.
Analysis of the symmetry of the brain hemispheres at the level of individual structures and dominant tissue features has been the subject of research for many years in the context of improving the effectiveness of imaging methods for the diagnosis of brain tumor, stroke, and Alzheimer's disease, among others. One useful approach is to reliably determine the midline of the brain, which allows comparative analysis of the hemispheres and uncovers information on symmetry/asymmetry in the relevant planes of, for example, CT scans. Therefore, an effective method that is robust to various geometric deformations, artifacts, varying noise characteristics, and natural anatomical variability is sought.
View Article and Find Full Text PDFBrain Inform
January 2025
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.
View Article and Find Full Text PDFCommun Med (Lond)
January 2025
Rare Disease Translational Center, The Jackson Laboratory, Bar Harbor, ME, USA.
Background: Multiple Sulfatase Deficiency (MSD) is a rare inherited lysosomal storage disorder characterized by loss of function mutations in the SUMF1 gene that manifests as a severe pediatric neurological disease. There are no available targeted therapies for MSD.
Methods: We engineered a viral vector (AAV9/SUMF1) to deliver working copies of the SUMF1 gene and tested the vector in Sumf1 knock out mice that generally display a median lifespan of 10 days.
Cell Death Differ
January 2025
Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Aging is a major risk factor for Alzheimer's disease (AD). With the prevalence of AD increased, a mechanistic linkage between aging and the pathogenesis of AD needs to be further addressed. Here, we report that a small ubiquitin-related modifier (SUMO) modification of p53 is implicated in the process which remarkably increased in AD patient's brain.
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