Molecular Classification
Other (protein aggregation/aggregate), Peptide/protein aggregate, Pathological aggregate
Other Names
Amyloid β aggregation, Beta-amyloid aggregation, Amyloid-beta aggregation, Amyloid beta-protein aggregation
Disease Roles
Neurodegenerative disease (specifically Alzheimer’s disease and cerebral amyloid angiopathy)[2][3][5]Other (potentially implicated in cognitive decline and rare amyloidopathies)

Amyloid beta aggregation Overview

Amyloid beta aggregation refers to the misfolding and assembly of amyloid beta (Aβ) peptides, primarily 36–43 amino acids in length, into soluble oligomers, protofibrils, and insoluble amyloid fibrils. This process is central to the pathology of Alzheimer’s disease, where aggregated Aβ forms the extracellular amyloid plaques observed in the brain[2][3][5]. Aggregation is driven by a nucleation-dependent pathway with conformational conversion of Aβ monomers into beta-sheet-rich structures, leading to a spectrum of assemblies—soluble oligomers are now considered the most neurotoxic species, while fibrillar plaques are pathologically diagnostic[6][7]. Therapeutic targeting of amyloid beta aggregation aims to remove or neutralize these toxic species, but challenges include the physiological functions of Aβ—such as synaptic modulation, antimicrobial roles, and response to brain injury—and the substantial safety risks observed with anti-amyloid therapies (notably ARIA and infections)[4][5]. Numerous monoclonal antibodies and small molecules have been developed to inhibit aggregation, promote clearance, or selectively bind toxic oligomers[3]. Reliable biomarkers for amyloid aggregation are crucial for diagnosis, patient selection, and monitoring efficacy of therapy; these include PET tracers, CSF/plasma ratios of Aβ, and emerging oligomer-selective assays[3][6]. Despite being a key therapeutic target, amyloid beta aggregation remains a focus of intensive research due to challenges in differentiating pathological from physiological aggregation and mitigating associated risks.

Mechanism of Action

Monoclonal antibody–mediated clearance of amyloid beta aggregates (e.g. Aducanumab, Lecanemab)[3] Stabilization or prevention of oligomer formation (solanezumab, tramiprosate) Promotion of amyloid beta degradation/clearance Inhibition of amyloid beta aggregation

Biological Functions

Protein misfolding and aggregation
Formation of amyloid plaques
Neurotoxicity (toxic oligomer formation)
Potential involvement in pathogen defense, blood-brain barrier repair, and synaptic regulation in physiological contexts[4]

Disease Associations

Neurodegenerative disease (specifically Alzheimer’s disease and cerebral amyloid angiopathy)[2][3][5]
Other (potentially implicated in cognitive decline and rare amyloidopathies)

Safety Considerations

  • Amyloid-related imaging abnormalities (ARIA, including edema and microhemorrhages)
  • Increased risk of brain infections (potential loss of antimicrobial activity)
  • Potential cognitive/neurological worsening in some individuals
  • Unintended impairment of physiological roles of amyloid beta (e.g., synaptic regulation, BBB repair)[4]

Interacting Drugs

Aducanumab
Lecanemab
Donanemab
Solanezumab
Bapineuzumab
Tramiprosate
IVIG (intravenous immunoglobulin, investigational)
Other anti-amyloid antibodies in research/clinical trials[3]

Associated Biomarkers

Biomarker
Amyloid PET imaging tracers (e.g., Pittsburgh Compound B, florbetapir)
Cerebrospinal fluid (CSF) Aβ42 (decreased in AD)
Plasma Aβ42/40 ratio
Soluble oligomer-selective assays (e.g., SOBA as research tool)[3][6]