Phosphorylated proteins play important roles in the pathogenesis of Alzheimer's disease (AD). The most abundant constituent in AD's brain deposit is the amyloid-β₄₀ peptide (Aβ₄₀). Based on it, the degree of phosphorylated Aβ₄₀ in body fluids (e.g., cerebrospinal fluid, CSF), which is defined by the ratio of phosphorylated Aβ₄₀ to total Aβ₄₀ (pAβ₄₀/tAβ₄₀), is anticipated to be an index for early diagnosis of AD. The major challenge in pAβ₄₀/tAβ₄₀ detection is the large concentration difference between two Aβ₄₀ forms in the real samples, which usually requires multichannel equipment and complicated detection process. In this paper, we revealed the unexpected close affinities of the anti-Aβ₄₀ antibody to Aβ₄₀ (40.2 nM^-1) and to pAβ₄₀ (42.3 nM^-1). Based on it, a convenient coimmunocapture and electrochemical quantitation of tAβ₄₀ and pAβ₄₀ was achieved on an anti-Aβ₄₀ antibody immobilized Au electrode (anti-Aβ₄₀/Au). Once Aβ₄₀ and pAβ₄₀ were synchronously captured on the anti-Aβ₄₀/Au electrode, the tAβ₄₀ levels in CSF samples were quantified with electrochemical impedance spectroscopy. With the signal amplification from Cd²⁺/Ti⁴⁺-functionalized titanium phosphate nanospheres (Cd²⁺/Ti⁴⁺@TiP) which was selective conjugated to pAβ₄₀, concentrations of low abundant pAβ₄₀ as low as 1 fM were readily measured by square wave voltammetry. Our results reveal that despite the concentrations of tAβ₄₀ and pAβ₄₀ fluctuate in each individual case, the concentration ratios of pAβ₄₀/tAβ₄₀ in CSF samples from AD patients are significant larger than those from healthy donors. It demonstrates that the degree of phosphorylated Aβ₄₀ is hopeful to be an effective index for evaluating the AD progress and improving the accuracy of clinic AD diagnosis.

#	Concept	H-Index	Publications	Citations
1	Health Sciences	1	1	102
2	Medicine	1	1	102
3	Pathology	1	1	102
4	Epigenetics	1	1	102
5	Cancer Research	1	1	102

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