Amyloid Beta in Aging and Alzheimer's Disease

• Published in: International journal of molecular sciences Vol. 23; no. 21; p. 12924
• Main Authors: Sehar, Ujala, Rawat, Priyanka, Reddy, Arubala P, Kopel, Jonathan, Reddy, P Hemachandra
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26-10-2022; MDPI
• Subjects: Aged; Aging; Alzheimer Disease - metabolism; Alzheimer's disease; amyloid beta; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein; Amyloid Precursor Protein Secretases - metabolism; Animal cognition; Astrocytes; Cognitive ability; Dementia; Diabetes; Disease Progression; Etiology; Genes; Genetic factors; Geriatrics; Global economy; Glycoproteins; Homeostasis; Humans; Intracellular signalling; Memory; Metabolism; Microglia; Mitochondria; Mortality; Mutation; Neurodegenerative Diseases; neurofibrillary tangle; Older people; Pathogenesis; Peptides; Presenilin 1; Presenilin 2; Proteins; Proteolysis; Review; Risk factors; Signal transduction; Structure-function relationships; Synapses; Tau protein; therapeutics; Traumatic brain injury; β-Amyloid; therapeutics; Alzheimer’s disease; amyloid precursor protein; mitochondria; amyloid beta; neurofibrillary tangle
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232112924

Alzheimer's disease (AD), is a progressive neurodegenerative disease that affects behavior, thinking, learning, and memory in elderly individuals. AD occurs in two forms, early onset familial and late-onset sporadic; genetic mutations in PS1, PS2, and APP genes cause early onset familial AD, and a combination of lifestyle, environment and genetic factors causes the late-onset sporadic form of the disease. However, accelerated disease progression is noticed in patients with familial AD. Disease-causing pathological changes are synaptic damage, and mitochondrial structural and functional changes, in addition to increased production and accumulation of phosphorylated tau (p-tau), and amyloid beta (Aβ) in the affected brain regions in AD patients. Aβ is a peptide derived from amyloid precursor protein (APP) by proteolytic cleavage of beta and gamma secretases. APP is a glycoprotein that plays a significant role in maintaining neuronal homeostasis like signaling, neuronal development, and intracellular transport. Aβ is reported to have both protective and toxic effects in neurons. The purpose of our article is to summarize recent developments of Aβ and its association with synapses, mitochondria, microglia, astrocytes, and its interaction with p-tau. Our article also covers the therapeutic strategies that reduce Aβ toxicities in disease progression and discusses the reasons for the failures of Aβ therapeutics.