Gosset Beta-amyloid fibril Overview
Beta-amyloid fibrils are insoluble, highly ordered protein aggregates composed of amyloid-beta (Aβ) peptides, most commonly Aβ(1–40) or Aβ(1–42), produced by proteolytic cleavage of amyloid precursor protein[3][1]. These fibrils display a characteristic "cross-β" structure: β-sheet planes arrayed parallel to the fibril axis, with β-strands perpendicular to it[1][7]. Aβ fibril formation is a hallmark pathological feature of Alzheimer's disease (AD), contributing to amyloid plaques in brain tissue[4][3]. They are implicated in neurotoxicity, neuroinflammation, and synaptic loss in AD, though intermediate Aβ aggregates (oligomers and protofibrils) may have additional distinct toxicities[2][8]. Therapeutic efforts target fibril clearance, formation inhibition, or disaggregation—primarily via monoclonal antibodies or small molecules. Safety challenges include inflammatory reactions (such as ARIA) and incomplete knowledge regarding which Aβ assemblies are most relevant to disease progression[4][2][6].
Mechanism of Action
Antibody-mediated clearance (immunologically targets and removes Aβ fibrils or protofibrils); Inhibition of fibril formation (blocks aggregation or seed formation); Disaggregation (promotes breakdown of existing fibrils)
Biological Functions
Disease Associations
Safety Considerations
- Amyloid-related imaging abnormalities (ARIA, including edema and microhemorrhage) with immunotherapies
- Off-target immune activation/inflammation
- Cognitive worsening in some patients with anti-amyloid therapies
- Unintended increases in vascular amyloid (cerebral amyloid angiopathy risk)
Interacting Drugs
Associated Biomarkers
| Biomarker |
|---|
| Amyloid PET (positron emission tomography) imaging using tracers (detects Aβ aggregates) |
| Cerebrospinal fluid (CSF) Aβ42/40 ratio |
| Plasma Aβ42/40 |