01
The barrier blocks it屏障横断
Only about 0.1% of a systemically dosed antibody crosses the intact blood-brain barrier, so most of the drug never reaches the brain.全身给药之抗体，仅千分之一能越血脑屏障。余者，皆不得其门而入。
Zuchero et al., Neuron, 2016Zuchero et al., Neuron, 2016
02
The brain reacts脑内激变
Anti-amyloid antibodies commonly trigger ARIA, brain swelling and microbleeds. At the top dose, incidence ranges from roughly 10% to over 40%, with reported fatalities.抗淀粉样蛋白抗体常诱发 ARIA，脑水肿、微出血并见。极量之下，发病率自一成至四成不等，更有致死之报。
Withington & Turner, Front. Neurol., 2022Withington & Turner, Front. Neurol., 2022
03
One target is not enough单靶难济
Alzheimer's and Parkinson's are driven by many pathways at once, and single-target therapies have repeatedly failed to change their course.阿尔茨海默与帕金森，乃多途并驱之疾。单靶疗法，屡战屡败，终难撼其势。
Cummings et al., Alz & Dement TRCI, 2020Cummings et al., Alz & Dement TRCI, 2020