Calcium ion (Ca2+)

Calcium ions (Ca2+) are critical physiological messengers that play a dual role in the pathology of amyloid diseases, acting as both a structural component of deposits and a mediator of cellular toxicity. In neurodegenerative conditions like Alzheimer's disease, calcium is sequestered within amyloid-beta (Aβ) plaques, where it stabilizes the fibrillar architecture and catalyzes the formation of neurotoxic oligomers (1, 8, 14). This interaction facilitates a feed-forward cycle of toxicity: amyloid aggregates disrupt membrane integrity to allow excessive calcium influx, which in turn promotes further amyloid aggregation and neuronal death (2, 11). In systemic amyloidosis, particularly cardiac transthyretin (TTR) amyloidosis, the presence of calcium within amyloid deposits is exploited for diagnostic purposes. Bone-seeking radiopharmaceuticals, such as Technetium-99m pyrophosphate, specifically bind to these calcium-containing deposits, allowing for non-invasive imaging and differentiation of amyloid subtypes (16, 18). While calcium itself is not a primary therapeutic target, pharmacological intervention typically focuses on modulating its signaling via NMDA receptor antagonists or ryanodine receptor modulators to mitigate the downstream effects of calcium dyshomeostasis (3, 10, 13).

Other names

Ca2+Calcium cationAmyloid-associated calciumCalcified amyloid depositsExtracellular calcium

Calcium ions interact with acidic residues of amyloidogenic proteins to promote aggregation and stabilize the cross-beta sheet structure of fibrils (6, 8). In diagnostic imaging, phosphate-based radiotracers form complexes with the crystalline or amorphous calcium found in amyloid deposits to visualize organ involvement (12, 16).