Novel AβIsoforms in Alzheimer's Disease - Their Role in Diagnosis and Treatment
Erik Portelius, Niklas Mattsson, Ulf Andreasson, Kaj Blennow and Henrik Zetterberg
Affiliation: Clinical Neurochemistry Laboratory Institute of Neuroscience Sahlgrenska University Hospital,Molndal SE-431 80 Molndal Sweden.
Keywords: Alzheimer's disease, Amyloid, APP, biomarker, theragnostic marker, Abeta-degrading enzymes, Down's syndrome, mass spectrometry, amino acid, Western blot, Subventricular Zone (SVZ) Derived Oligodendrogenesis, Activated Astrocytes and Microglia, Remyelination, Molecular Therapies, Adult Neural Stem/Progenitor Cells (NPCs), Adult Mesenchymal Stem Cells (MSCs), Cell Transplantation, Immunemodulation, T and B Cells, Lymph Nodes, Blood Brain Barrier (BBB), Neuroprotection, Regeneration, Therapeutic Plasticity
The last decades have witnessed an explosion in studies of the role of amyloid-β (Aβ) in the progress of the neurodegenerative disorder Alzheimer´s disease (AD) and it is now widely accepted that Aβ is related to the pathogenesis of AD. For example, studies have shown that Aβ is neurotoxic and that the neurotoxicity of Aβ is related to its aggregation state. The concentration of the 42 amino acid form of Aβ (Aβ1-42) is reduced in the cerebrospinal fluid (CSF) from AD patients, which is believed to reflect the AD pathology with plaques in the brain acting as sinks. Less well investigated, however, is the ability of other Aβ isoforms to distinguish AD patients from controls and to identify treatment effects in clinical trials. Recently, novel C-truncated forms of Aβ (Aβ1-14, Aβ1-15, and Aβ1-16) were identified in human CSF. The presence of these small peptides is consistent with a catabolic amyloid precursor protein cleavage pathway by β- followed by α-secretase. It has been shown that Aβ1-14, Aβ1-15, and Aβ1-16 increase dose-dependently in response to γ-secretase inhibitor treatment while Aβ1-42 levels are unchanged. Here, we review the many aspects of Aβ and its isoforms with special focus on their potential role as diagnostic and theragnostic markers.
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