Alzheimer's disease-related proteins

Alzheimer's disease-related proteins refer to a heterogeneous group of molecules central to the pathogenesis of Alzheimer's disease (AD), primarily characterized by the accumulation of amyloid-beta (Aβ) plaques and tau-containing neurofibrillary tangles (Hardy & Higgins, 1992; Jack et al., 2018). Amyloid-beta is produced through the sequential cleavage of Amyloid Precursor Protein (APP) by BACE1 and gamma-secretase, while tau protein undergoes hyperphosphorylation, leading to microtubule destabilization and neuronal death (Vassar et al., 1999). Other critical proteins include Apolipoprotein E (APOE), which modulates Aβ clearance, and various neurotransmitter receptors like the NMDA receptor and acetylcholinesterase, which are targeted for symptomatic relief (Corder et al., 1993). Therapeutic strategies have evolved from symptomatic treatments like Donepezil to disease-modifying therapies such as Lecanemab and Aducanumab, which aim to reduce the amyloid burden (van Dyck et al., 2023). Despite these advancements, drug development remains challenging due to the blood-brain barrier, the complexity of neuroinflammatory pathways, and significant side effects such as Amyloid-Related Imaging Abnormalities (ARIA) (Sperling et al., 2011). Emerging research also focuses on neuroinflammatory targets like TREM2 and the role of neurofilament light chain as a marker of axonal damage (Colonna & Wang, 2016).

Other names

AD-related proteinsAlzheimer's disease targetsAmyloidogenic proteinsTauopathy-related proteinsAlzheimer's disease biomarkers

The mechanisms of action for drugs targeting these proteins include the inhibition of acetylcholinesterase to increase synaptic acetylcholine levels, antagonism of NMDA receptors to reduce excitotoxicity, and the use of monoclonal antibodies to facilitate the clearance of amyloid-beta plaques from the brain (Hardy & Higgins, 1992; van Dyck et al., 2023). Additionally, experimental approaches have targeted beta-secretase (BACE1) and gamma-secretase to prevent the formation of amyloid-beta peptides (Vassar et al., 1999).