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Amyloid precursor protein in platelets: a peripheral marker for the diagnosis of sporadic AD
A Padovani1, L Pastorino, B Borroni
1Dipt. Scienze Mediche e Chirurgiche, Unità di Neurologia, Università degli Studi di Brescia, Italy. padovani@bshosp.osp.unibs.it
Background:
An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD.
Objective:
To evaluate the sensitivity and the specificity of platelet APP forms' ratio (APPr) as a marker for AD.
Methods:
Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands.
Results:
Mean APPr levels were decreased in AD patients (mean OD +/- SD = 0.35 +/- 0.18) compared with the CON group (mean OD +/- SD = 0.92 +/- 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05).
Conclusion:
Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.
Insights
The ratio of amyloid precursor protein (APP) forms in platelets can help diagnose Alzheimer's disease (AD). This platelet APP ratio (APPr) shows high accuracy in distinguishing AD from other conditions.
Area of Science:
- Biochemistry
- Neuroscience
- Medical Diagnostics
Background:
- Altered amyloid precursor protein (APP) forms are observed in Alzheimer's disease (AD) patients' platelets.
- A reduced ratio between upper (130 kDa) and lower (106-110 kDa) APP immunoreactivity bands is a key indicator.
Purpose of the Study:
- To determine the sensitivity and specificity of the platelet APP forms ratio (APPr) as a diagnostic marker for AD.
- To assess the utility of APPr in differentiating AD from normal aging and other neurological disorders.
Main Methods:
- Western Blot analysis and immunostaining were used to evaluate platelet APPr in 85 probable AD patients and 95 controls.
- APPr was calculated as the ratio of optical densities between the upper and lower APP immunoreactive bands.
Main Results:
- Mean APPr levels were significantly lower in AD patients (0.35 +/- 0.18) compared to controls (0.92 +/- 0.38) (p < 0.0001).
- Receiver Operating Curve analysis indicated a cut-off of 0.57 yielded 88.2% sensitivity and 89.4% specificity (AUC=0.945).
- APPr levels correlated significantly with AD disease severity.
Conclusions:
- Platelet APPr effectively differentiates AD from normal aging and other dementing disorders with high accuracy.
- Platelet APPr shows potential as an adjunctive diagnostic tool in clinical settings for AD.