Amyloid-beta aggregation implicates multiple pathways in Alzheimer's disease: Understanding the mechanisms

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
• It is characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau.
• AD leads to neuronal damage, synaptic dysfunction, and cognitive deficits.

Purpose of the Study:

• To review the molecular mechanisms of Aβ aggregation in Alzheimer's disease.
• To highlight the role of secretase enzymes in Aβ production.
• To discuss the downstream effects of Aβ aggregation on tau pathology and neurotransmitter systems.

Main Methods:

• Literature review of molecular mechanisms in Alzheimer's disease.
• Analysis of the role of beta (β) and gamma (γ) secretases in amyloid precursor protein (APP) hydrolysis.
• Examination of the link between Aβ aggregation, oxidative stress, inflammation, and tau hyperphosphorylation.

Main Results:

• Aβ aggregation is initiated by APP hydrolysis via β- and γ-secretases.
• Aβ fibrils trigger oxidative stress, inflammation, and caspase activation, leading to tau hyperphosphorylation and NFT formation.
• Acetylcholinesterase (AChE) activity contributes to acetylcholine deficiency and cognitive impairment.

Conclusions:

• Current Alzheimer's disease treatments lack disease-modifying efficacy.
• Further research is crucial for developing novel therapeutic compounds.
• Future clinical trials may explore multi-target agents addressing amyloid, tau, neuroinflammation, and neurotransmitter modulation.