The amyloid precursor protein (APP) plays a central role in the pathophysiology of Alzheimer's disease in large part due to the sequential proteolytic cleavages that result in the generation of β-amyloid peptides (Aβ). Not surprisingly, the biological properties of APP have also been the subject of great interest and intense investigations. Since our 2006 review, the body of literature on APP continues to expand, thereby offering further insights into the biochemical, cellular and functional properties of this interesting molecule. Sophisticated mouse models have been created to allow in vivo examination of cell type-specific functions of APP together with the many functional domains. This review provides an overview and update on our current understanding of the pathobiology of APP.
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http://dx.doi.org/10.1186/1750-1326-6-27 | DOI Listing |
Cureus
December 2024
Department of Physiology, Touro College of Osteopathic Medicine, Middletown, USA.
Down syndrome (DS) is a genetic intellectual disorder caused by trisomy of chromosome 21 (Hsa21) and presents with a variety of phenotypes. The correlation between the chromosomal abnormality and the resulting symptoms is unclear, partly due to the spectrum of impairments observed. However, it has been determined that trisomy 21 contributes to neurodegeneration and impaired neurodevelopment resulting from decreased neurotransmission, neurogenesis, and synaptic plasticity.
View Article and Find Full Text PDFDown syndrome, resulting from trisomy of human chromosome 21, is a common form of chromosomal disorder that results in intellectual disability and altered risk of several medical conditions. Individuals with Down syndrome have a greatly increased risk of Alzheimer's disease (DSAD), due to the presence of the APP gene on chromosome 21 that encodes the amyloid-β precursor protein (APP). APP can be processed to generate amyloid-β, which accumulates in plaques in the brains of people who have Alzheimer's disease and is the upstream trigger of disease.
View Article and Find Full Text PDFActa Neuropathol
January 2025
Department of Clinical Sciences, Lund Brain Injury Laboratory for Neurosurgical Research, Lund University, 222 20, Lund, Sweden.
Traumatic brain injury (TBI) often leads to impaired regulation of cerebral blood flow, which may be caused by pathological changes of the vascular smooth muscle cells (VSMCs) in the arterial wall. Moreover, these cerebrovascular changes may contribute to the development of various neurodegenerative disorders such as Alzheimer's-like pathologies that include amyloid beta aggregation. Despite its importance, the pathophysiological mechanisms responsible for VSMC dysfunction after TBI have rarely been evaluated.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050, P. R. China.
MicroRNAs (miRNAs) are associated with amyloid-β (Aβ) dysmetabolism, a pivotal factor in the pathogenesis of Alzheimer's disease (AD). This study unveiled a novel miRNA, microRNA-32533 (miR-32533), featuring a distinctive base sequence identified through RNA sequencing of the APPswe/PSEN1dE9 (APP/PS1) mouse brain. Its role and underlying mechanisms were subsequently explored.
View Article and Find Full Text PDFJ Toxicol Pathol
January 2025
Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa 252-5201, Japan.
Amyloidosis is characterized by the extracellular deposition of insoluble protein fibrils that cause cellular damage and dysfunction in organs and tissues. Multiple types of amyloidosis and their causative precursor proteins have been identified in humans and animals. In toxicological studies, a high incidence of spontaneous amyloidosis has been reported in CD-1 mice; however, the precursor protein responsible remains unclear.
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